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Molecular mechanisms of the microRNA-132 during tumor progressions

Cancer Cell International volume 21, Article number: 439 (2021) Cite this article

Abstract

Cancer as one of the leading causes of human deaths has always been one of the main health challenges in the world. Despite recent advances in therapeutic and diagnostic methods, there is still a high mortality rate among cancer patients. Late diagnosis is one of the main reasons for the high ratio of cancer related deaths. Therefore, it is required to introduce novel early detection methods. Various molecular mechanisms are associated with the tumor progression and metastasis. MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) family that has important functions in regulation of the cellular processes such as cell proliferation, apoptosis, and tumor progression. Moreover, they have higher stability in body fluids compared with mRNAs which can be introduced as non-invasive diagnostic markers in cancer patients. MiR-132 has important functions as tumor suppressor or oncogene in different cancers. In the present review, we have summarized all of the studies which have been reported the role of miR-132 during tumor progressions. We categorized the miR-132 target genes based on their cell and molecular functions. Although, it has been reported that the miR-132 mainly functions as a tumor suppressor, it has also oncogenic functions especially in pancreatic tumors. MiR-132 mainly exerts its roles during tumor progressions by regulation of the transcription factors and signaling pathways. Present review clarifies the tumor specific molecular mechanisms of miR-132 to introduce that as an efficient non-invasive diagnostic marker in various cancers.

Background

Cancer is one of the main causes of human deaths worldwide, with an estimated 10.0 million deaths in 2020 [1]. It is the second leading cause of mortality in the United States with about 606,520 deaths in 2020 [2, 3]. The financial burden of cancer poses different challenges for the patients and healthcare system [4]. As the morphologically similar tumors may exhibit different clinical symptoms due to their molecular differences, it is of high importance to introduce non-invasive methods to assess the molecular differences in tumors to select the most efficient therapeutic option. As the non-protein-coding DNA covers almost 97% of the human genome, non-coding RNAs (ncRNAs) have become the frontier of cancer biology [5, 6]. They are categorized into the various families such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), small interfering RNAs (siRNAs), and circular RNA (circRNA) [7,8,9]. MiRNAs are a class of the short ncRNAs involved in post-transcriptional regulation through binding to 3 untranslated region (3-UTR) of the target mRNA that results in mRNA degradation or translational inhibition [10]. Considering, the crucial functions of miRNAs in regulation of cellular mechanisms including cell proliferation, differentiation, growth, and apoptosis [11, 12], aberrant miRNA expression can be correlated with various cancers [13]. MiRNAs may serve as tumor suppressors, oncogenes, and regulators of the self-renewal process in cancer stem cells (CSC) [14]. Dysregulated miRNAs are promising diagnostic tumor markers and are also efficient as novel targets for the cancer therapy [15]. Since, they have higher stability in body fluids compared with mRNAs, the expression profiling of circulating miRNAs in body fluids can be utilized as a non-invasive method for cancer diagnosis and prognosis [16,17,18,19,20]. MiR-132 is a critical regulator of various cellular processes such as angiogenesis, cell proliferation, migration, and apoptosis [21,22,23]. Aberrant expression of miR-132 has been frequently reported in various cancers. It functions as a tumor suppressor or oncogene in different cancers [24,25,26,27]. Therefore, we have summarized all of the studies which have been reported the role of miR-132 during tumor progressions. We categorized the miR-132 target genes based on their cell and molecular functions (Table 1).

Table 1 Molecular targets of miR-132 during tumor progressions
Full size table

Transcription factors

Forkhead box proteins (Fox) transcription factors

There are increasing numbers of the feedback loop interactions between transcription factors and miRNAs in which the transcription factors up or down regulate the miRNAs, while the miRNAs inhibit the transcription factors in a negative feedback [28]. FOXO1 belongs to the Forkhead box proteins (Fox) transcription factors that functions as a negative regulator of cell cycle progression [29]. It has been shown that miR-132 significantly promoted gastric tumor cell growth by FOXO1 targeting. There was also significant miR-132 up regulation in gastric cancer (GC) tissues in comparison with normal margins [30]. Forkhead box protein A1 (FOXA1) is a pivotal transcription factor involved in cell proliferation, apoptosis, and differentiation, organogenesis, and tumor progression [31, 32]. It is required for the chromatin recruitment of estrogen receptor that regulates chromatin remodeling, estrogen receptor-related gene expressions, and tumor cell proliferation [33, 34]. It has been shown that there was an inverse correlation between the levels of miR-132 and FOXA1 expressions. MiR-132 reduced the breast tumor cells proliferation via FOXA1 targeting [35]. There was also miR-132 down regulation in thyroid tumor tissues and cell lines. It reduced thyroid tumor cell proliferation and invasion by FOXA1 inhibition [36]. Cisplatin (CDPP) is one of the main therapeutic drugs in nasopharyngeal carcinoma (NPC), however there is a noticeable ratio of resistance among the patients [37]. It has been reported that there was miR-132 down regulation in NPC patients. It also induced CDDP sensitivity in NPC cells through FOXA1 suppression [32]. Long non-coding RNAs (lncRNAs) are a family of the ncRNAs that regulate cell growth and tumorigenesis by post-transcriptional regulation and miRNAs sponging [38]. They are involved in tumorigenesis, tissue development, embryogenesis, and inflammation [39,40,41]. Pseudogene belongs to the lncRNAs family that regulates the gene expression during tumor progressions. PTTG3P is a pseudogene that is up regulated in pancreatic ductal adenocarcinoma (PDAC) tissues. It has been observed that there were correlations between the PTTG3P up regulation, larger tumor size, poor prognosis, and poor differentiation in PDAC tissues. PTTG3P induced tumor growth and invasion through miR-132-3p sponging that resulted in FOXM1 targeting [42]. It has been observed that there were LINC01551 up regulation in NPC tissues and cells. LINC01551 induced malignant transformation of NPC by miR-132-5p sponging [43].

Developmental transcription factors

SOX5 belongs to the Sox family of developmental transcription factors involved in regulation of embryogenesis, cell differentiation, proliferation, and migration [44]. There were miR-132 down regulations in invasive pituitary tumor tissues and cell lines. It reduced cell proliferation and invasion through SOX5 suppression [45]. Circular RNAs (CircRNAs) are endogenous RNAs characterized by closed continuous loops without polyadenylated tail [46]. They are involved in different cellular mechanisms such as chromatin remodeling, cell proliferation, apoptosis, invasion, and differentiation [47, 48]. It has been observed that there was circDOCK1 up regulation in bladder cancer (BCa) cells. CircDOCK1 induced cell proliferation and migration by miR‐132‐3p sponging that resulted in SOX5 up regulation [49]. SOX2 is a developmental transcription factor that participates in self-renewal process and tumor progression [50]. NEAT1 sponged miR-132 to up regulate SOX2 in glioma cells [51]. Epithelial-mesenchymal transition (EMT) is a pivotal process during tumor progression in which the tumor cells lose their epithelial feature and cell–cell adhesion to gain mesenchymal feature with high migratory and invasive properties [52,53,54]. EMT is orchestrated by various structural factors such as CDH1 and VIM that are regulated by EMT-related transcription factors including SNAI1, SNAI2, and TWIST [55,56,57]. SOX4 is a developmental transcription factor with critical functions during embryogenesis and tumorigenesis. It has been shown that miR-132 reduced osteosarcoma (OS) cell proliferation and EMT via SOX4 targeting. There was a miR-132 down regulation in OS cell lines in comparison with normal cells. It also regulated apoptosis by BCL-2 targeting. Moreover, miR-132 significantly inhibited OS invasion by CDH1 up regulation, while down regulation of the mesenchymal factors such as CDH2 and VIM [58]. SOX4 has a critical role in promotion of EMT process during the prostate cancer (PCa) progression [59]. There was a significant association between miR-132 down regulation, high Gleason score, and distant metastasis. MiR-132 inhibited prostate tumor cell migration, colony formation, and TGF-b-induced EMT by SOX4 targeting [60]. Other studies have been reported that miR-132-3p inhibited the lung and liver tumor cells invasions by SOX4 targeting [61, 62]. E2F5 belongs to the E2F family of transcription factors that regulate cell cycle progression [63]. It has been observed that there were significant miR-132 down regulation in ovarian tumor tissues and cell lines. It suppressed ovarian tumor cell proliferation and invasion via E2F5 targeting [64]. SIRT1 is an NAD dependent deacetylase that regulates cell death in oxidative and genotoxic stresses [65, 66]. SREBP is a leucine zipper transcription factor involved in cholesterogenesis and lipogenesis [67]. It has been observed that miR-132 reduced glioma cell proliferation by down regulations of SIRT1 and SREBP-1c [68]. CAMP-responsive element binding protein 5 (CREB5) is a zinc-finger DNA-binding protein with pivotal functions in cell proliferation and differentiation [69]. There was a significant SNHG5 up regulation in colorectal cancer (CRC) cells. It induced CRC invasion, while inhibited apoptosis through CREB5 up regulation following the miR-132-3p sponging [70].

EMT-related transcription factors

Enhancer of zeste homolog 2 (EZH2) is one of the components of Polycomb repressor complex 2 (PRC2) that is involved in DNA methylation using DNA methyl transferases (DNMTs) recruitment [71]. It has a pivotal role in epigenetic silencing by catalyzing the H3K27me3 in promoter sequences [72]. EZH2 is also up regulated by various transcription factors like SOX4 [73]. It has been reported that the SOX4/EZH2 complex induced H3K27me3 in miR-132 promoter sequence. MiR-132 reduced EMT process in ovarian tumor cells by CDH1 up regulation, while CDH2 and VIM down regulations. Therefore, SOX4 was suggested as the effector of miR-132 during EMT regulation in ovarian cancer (OC) [74]. BMI-1 is a ring finger component of PRC1 complex involved in epigenetic suppression [75]. It is an epigenetic modification protein involved in CSC self-renewal, tumor progression, and metastasis [21]. There were correlations between the BMI-1 up regulation, poor prognosis, increased invasion, and radio resistance [76, 77]. It was observed that there was miR-132 down regulation in cervical cancer. There was also a direct association between the levels of miR-132 expressions and radiation intensity. MiR-132 increased radio sensitivity through BMI-1 targeting [78]. It has been shown that there was significant miR-132 down regulation in SKOV3/CDDP cells compared with maternal SKOV3 cells. Reduced levels of miR-132 induced the CDDP resistance in ovarian tumor cells via BMI-1 targeting and subsequent apoptosis inhibition [79]. ZEB2 is a zinc finger transcription factor that functions as a transcriptional co-repressor via R-SMADs binding. There were significant SOX2OT up regulations in Non-small-cell lung carcinoma (NSCLC) tissues and cell lines. SOX2OT silencing significantly reduced cell proliferation, invasion, and EMT process by miR-132 sponging that resulted in ZEB2 up regulation [80]. There was also a significant miR-132 down-regulation in metastatic CRC tissues in comparison with non-metastatic tumor tissues. It reduced the CRC invasion and EMT process via ZEB2 targeting. The levels of miR-132 expressions were inversely correlated with stage, tumor size, survival, and distant metastasis in CRC patients [81].

Structural factors

USP9X belongs to the ubiquitin-specific peptidase (USP) family involved in various cellular processes via deubiquitinaton and stabilization of target proteins. USP9X up regulation is associated with tumor cell proliferation, drug resistance, and invasion [82]. It also deubiquitinates the MCL1 as an anti-apoptotic factor to suppress cell death in NSCLC [83]. It has been reported that miR-132 reduced NSCLC invasion via USP9X targeting [84]. USP22 belongs to the deubiquitinating enzyme (DUB) family of proteins involved in tumor relapse and progression [85]. USP22 silencing inhibits the tumor cell proliferation [76]. It has been reported that SNHG16 induced colorectal tumor cell proliferation and invasion through miR-132-3p sponging and subsequent USP22 up regulation [86]. HN1 promotes the ubiquitin-related degradation of b-catenin that results in loss of CDH1 interaction, actin organization, and cell migration [87]. It has been reported that there was miR-132 down regulation in breast cancer (BC) tissues in comparison with normal margins. MiR-132 significantly inhibited BC cell proliferation and metastasis through HN1 targeting. There was also a direct association between the levels of HN1 expression and poor survival in BC patients [23].

Derlin1 belongs to the derlin protein family that participates in endoplasmic reticulum (ER)-related degradation of misfolded proteins. It mediates retro translocation of misfolded proteins from ER to cytoplasm for the proteasomal degradation. Myocardial infarction associated transcript (MIAT) is an lncRNA associated with various human disorders such as diabetes and cancer [88]. There were significant MIAT up regulations in CRC tissues and cells. Silencing of MIAT promoted apoptosis, while suppressed CRC invasion. MIAT induced CRC cell proliferation and invasion through miR-132 sponging that resulted in Derlin-1 up regulation [89]. Tumor suppressor candidate 3 (TUSC3) is a component of the oligosaccharyl transferase complex involved in regulation of the N-linked protein glycosylation. It is a tumor suppressor frequently down regulated in different cancers. It has been reported that miR-132 promoted temozolomide resistance and glioblastoma initiating cells (GICs) phenotype formation by TUSC3 targeting in glioblastoma (GBM). TUSC3 also significantly down regulated the STAT3 and MDM2, while up regulate p53 [90].

TTK is a pivotal dual specificity kinase during mitotic checkpoint, centrosome duplication, and chromosome stability [91]. It induces cell proliferation and migration via AKT activation [92]. HLF is a transcription factor involved in resistance toward oxidative stress-induced apoptosis [93]. It has been reported that there were miR-132 down regulations in glioma tissues and cell lines that were associated with advanced tumor grades. HLF-mediated miR-132 inhibited glioma cell invasion and radio resistance via TTK inhibition [94]. P21-activated kinase 1 (Pak1) is a serine/threonine kinase that has key functions in cell migration, apoptosis, and neoplastic transformation [95, 96]. It regulates various cellular processes such as tumor cell invasion, drug resistance, angiogenesis, and EMT [97]. It exerts its oncogenic function by preventing apoptosis using different cascades including FOXO1, CLL/BCL-2, or DLC1 [98, 99]. ATF2 belongs to the b-ZIP family of transcription factors that regulates cellular differentiation and survival [100]. FN1 is an extracellular matrix glycoprotein involved in angiogenesis and tumor cell invasion [101]. It has been observed that miR-132 affected the hematogenous metastasis in GC. PAK1 down regulated the miR-132 via phosphorylation of ATF2 that prevents ATF2 to enter to the nucleus where it functions as an inducer of miR-132 expression. MiR-132 also reduced the levels of CD44 and FN1 expressions to promote lymphocytic mediated apoptosis of tumor cells. There were significant miR-132 down regulations in GC tissues that were associated with hematogenous metastasis. ATF2 up regulated the miR-132 that subsequently regulated the CD44/FN1/SIRT1/BDNF axis to recruit lymphocytes to suppress hematogenous metastasis in GC [102]. Receptor tyrosine kinases (RTKs) are the cell surface receptors for many extracellular signals such as hormones and growth factors. Aberrant RTK activation is implicated in progression of different tumors [103, 104]. MUC13 is a trans-membrane mucin associated with abnormal cell proliferation and tumor growth [105]. It activates the HER2, ERK, and AKT, while suppresses p53 expression [106]. It has been reported that there was a significant MUC13 up regulation in GC tissues in comparison with normal margins. MiR-132-3p suppressed GC progression by MUC13 targeting that resulted in activation of HER2 signaling [107].

Glucose transporter 1 (GLUT1) is a glucose uniporter across the erythrocytes plasma membranes. It has been shown that there was significant miR-132 down regulation in prostate tumor cells. MiR-132 silencing promoted the cell proliferation by induced glycolysis following the GLUT1 up regulation [108]. PEA-15 is an anti-apoptotic factor involved in TRAIL resistance of tumor cells. PEA15 over expression has been reported in GBM, leukemia, and NSCLC patients who were resistant against TRAIL [109,110,111]. MiR-132 reduced tumor cell proliferation and invasion, while increased apoptosis by targeting PEA-15 in astrocytoma. It was also observed that the miR-132 was regulated by CREB and KLF transcription factors [112]. Cyclin E1 (CCNE1) belongs to the cyclin family of proteins that regulates cyclin-dependent kinase 2 (CDK2) during cell cycle G1/S transition. It has been observed that there were miR-132 down regulations in OS tissues compared with normal bone tissues. MiR-132 reduced OS cell proliferation, colony formation, and in vivo growth via CCNE1 targeting [113].

PI3K/AKT pathway

The PI3K/AKT is an important signaling pathway that transfers the extracellular signals such as growth factors and hormones into the cells to regulate cell proliferation, metabolism, and apoptosis. PI3K activation by the RTKs and G-protein coupled receptors (GPCRs) subsequently phosphorylates and activates the AKT (Fig. 1). AKT is a serine/threonine kinase that has various effectors including CREB, FOXO, and mTOR [114, 115]. FOXO1 phosphorylation by AKT results in nuclear export and proteasome-dependent degradation [116]. It is a transcriptional regulator of apoptosis and CDK inhibitors such as BIM, FASL, p27, and p21 that inhibit G1/S transition and promote apoptosis [117, 118]. It has been reported that there was a significant miR-132 up regulation in laryngeal squamous cell carcinoma (LSCC) cells. MiR-132 promoted LSCC cell proliferation and tumor growth by PI3K/AKT activation and FOXO1 targeting [119]. PTEN as a tyrosine phosphatase inhibits the PI3K/AKT signaling by PIP3 dephosphorylation that results in AKT inhibition [120]. Therefore, PTEN down regulation activates the AKT/ERK pathway to regulate tumor cell proliferation and invasion. PTEN up regulation also promotes tumor cells apoptosis [121]. Moreover, it is a potent regulator of EMT progression [122]. It has been reported that there was miR-132 up regulation in pancreatic carcinoma that was associated with poor prognosis. MiR-132 reduced cell invasion and proliferation of pancreatic tumor cells through PTEN targeting [123]. MiR-132 increased doxorubicin resistance of BC cells through PTEN targeting [124]. Cold shock domain containing E1 (CSDE1) is an RNA binding protein (RBP) that is involved in tumor progression [125]. It has been observed that CSDE1 reduced thyroid tumor cell proliferation. CSDE1 down regulated the PTEN that resulted in AKT activation. MiR-132 also targeted the CSDE1 in thyroid tumor cells [126]. LAPTM4B is an inducer of tumor cell proliferation, invasion, and drug resistant by activation of PI3K/AKT pathway [127]. There were correlations between miR‐132‐3p down regulation, TNM staging, and tumor relapse in BC patients in which the patients with stage II/III had lower levels of miR-132-3p expressions compared with patients with stage I, and patients with recurrence had significantly lower levels of miR-132-3p expression. MiR‐132‐3p suppressed the breast tumor cell proliferation and invasion through LAPTM4B inhibition that resulted in inhibition of the PI3K/AKT/mTOR axis [128]. PIK3R3 is the regulatory subunit of the PI3K that phosphorylates phosphatidylinositol as a second messenger in intracellular signal transductions. It binds to the activated tyrosine kinases by SH2 domains to exert its functions. It has been reported that the LINC00160 knock down reduced the levels of PIK3R3 through miR-132 up regulation that resulted in reduced hepatocellular carcinoma (HCC) tumor cell drug resistance. There were also LINC00160 and PIK3R3 up regulations in HCC tissues. LINC00160 sponged the miR-132 to up regulate PIK3R3. LINC00160 silencing inhibited the HCC cell autophagy and proliferation, while induced apoptosis through PIK3R3 and ATG5 down regulations via promotion of miR-132 [129].

Fig. 1
figure 1

Molecular mechanisms of miR-132 in regulation of PI3K/AKT and MAPK and signaling pathways during tumor progression

Full size image

TGF-β pathway

Transforming growth factor b (TGF-β) is a secreted multi-faceted cytokine involved in regulation of embryogenesis, apoptosis, inflammation, and tissue homeostasis using SMAD family of transducer proteins. It triggers and maintains the EMT process by promotion of signaling pathways and transcription factors. Both SMAD-dependent and independent cascades are recruited by TGFβ to induce EMT during tumor progression. It has been reported that there was miR-132 down regulation in cervical cancer samples. MiR-132 reduced cervical tumor cell growth and invasion by SMAD2 targeting that resulted in EMT and cell cycle regulations. MiR-132 silencing promoted EMT via CDH1 down regulation, while VIM, FN1, SNAI1, SNAI2, and TWIST2 up regulations [130]. A significant miR-132 down regulation was also observed in BC tissues with metastatic lymph nodes. MiR-132 silencing promoted the breast tumor cell invasion and increased the levels of EMT-related markers and TGFβ1/SMAD2 expressions. There was an inverse association between SMAD2 and miR-132 expression levels in BC tissues. MiR-132 inhibited the EMT by down regulations of CDH2, ZEB1, SNAI1, and VIM in BC cells. It regulated the EMT process through TGFβ1/SMAD2 signaling pathway [131]. It has been observed that there was ILF3-AS1 up regulation in retinoblastoma (RB) tissues compared with normal controls. Levels of ILF3-AS1 expressions were directly correlated with advanced stage and optic nerve metastasis. ILF3-AS1 silencing significantly decreased malignant behaviors and in vivo tumor growth. ILF3-AS1 promoted RB progression through miR-132–3p sponging that up regulated the SMAD2 [132]. MiR-132 was reported to increase cisplatin sensitivity in Oral squamous cell carcinoma (OSCC) cells. There was also significant TGFβ1 up regulation in OSCC tissues that was conversely associated with miR-132 expression. MiR-132 also reduced OSCC cell proliferation and invasion by targeting the TGFβ1/SMAD2-3 axis [133]. Glucocorticoids are a class of corticosteroids with therapeutic values in lymphoid cancer, however some of the patients are insensitive to this treatment option [134]. Dexamethasone (DEX) is a glucocorticoid medication of tumor progression that promotes EMT and self-renewal via activation of the JNK and TGFβ pathways [135]. It has been observed that the DEX was involved in regulation of miR-132 promoter methylation. MiR-132 increased pancreatic tumor cell clonogenicity and EMT through TGFβ regulation [136].

Other signaling pathways

Mitogen-activated protein kinase (MAPK) signaling pathway is categorized to the ERK, JNK, and p38 cascades in mammalian cells which are involved in regulation of stress responses, cell proliferation, and differentiation. This signaling pathway transmits the extracellular signals via a sequential activation of MAP4K, MAP3K, and MAPKAPK. JNK and p38 are mainly activated in stress response, while the ERK1/2 are associated with cell proliferation and differentiation [137]. ERK1 is involved in tumor relapse, invasion, and drug resistance [138]. It can be regulated by the miR-132 during tumor progressions (Fig. 1). MiR-132 suppressed CRC cell proliferation and Adriamycin (ADM) resistance, while promoted apoptosis through ERK1 targeting [139]. There were XIST up regulations in CRC tissues and cells that were directly associated with TNM stage and tumor size. XIST induced colorectal tumor cell proliferation via the miR-132-3p/ERK2 axis [140]. Hedgehog (Hh) is a developmental signaling pathway involved in cell differentiation and embryogenesis. It is activated by Hh ligands binding with PTCH receptor that results in activation of GLI transcription factors [141]. Aberrant Shh activation induces the cell proliferation by Myc, PTCH, and CCND1 up regulations [142, 143]. It has been reported that miR-132 increased pancreatic tumor cell proliferation via Hh pathway [144]. Hippo signaling is involved in regulation of organ volume by the maintenance of cell proliferation/apoptosis balance [145, 146]. Yes-associated protein (YAP) is one of the key effectors of Hippo signaling pathway which has a pivotal function in induction of cell proliferation and invasion, while apoptosis suppression. It has been reported that miR-132 induced hepatoma cell apoptosis, while suppressed their proliferation and invasion through YAP targeting [147].

Conclusions

In present review we summarized all of the studies that have been evaluated the role of miR-132 in different cancers. This review clarifies the cell and molecular mechanisms that are regulated by miR-132 during tumor progressions. It has been reported that the miR-132 mainly functions as a tumor suppressor; it has also oncogenic functions especially in pancreatic tumors. It mainly exerts its roles during tumor progressions by regulation of the transcription factors and signaling pathways. Present review clarifies the tumor specific molecular mechanisms of miR-132 to introduce that as an efficient non-invasive diagnostic marker in various cancers.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

miRNAs:

MicroRNAs

ncRNAs:

Non-coding RNAs

lncRNAs:

Long noncoding RNAs

siRNAs:

Small interfering RNAs

circRNA:

Circular RNA

CSC:

Cancer stem cells

Fox:

Forkhead box proteins

FOXA1:

Forkhead box protein A1

NPC:

Nasopharyngeal carcinoma

BCa:

Bladder cancer

EMT:

Epithelial-mesenchymal transition

OS:

Osteosarcoma

PCa:

Prostate cancer

CREB5:

CAMP-responsive element binding protein 5

CRC:

Colorectal cancer

EZH2:

Enhancer of zeste homolog 2

PRC2:

Polycomb repressor complex 2

DNMTs:

DNA methyl transferases

OC:

Ovarian cancer

NSCLC:

Non-small-cell lung carcinoma

USP:

Ubiquitin-specific peptidase

MIAT:

Myocardial infarction associated transcript

TUSC3:

Tumor suppressor candidate 3

GICs:

Glioblastoma initiating cells

GBM:

Glioblastoma

Pak1:

P21-activated kinase 1

GLUT1:

Glucose transporter 1

CCNE1:

Cyclin E1

CDK2:

Cyclin-dependent kinase 2

GPCRs:

G-protein coupled receptors

LSCC:

Laryngeal squamous cell carcinoma

CSDE1:

Cold shock domain containing E1

RBP:

RNA binding protein

HCC:

Hepatocellular carcinoma

TGF-β:

Transforming growth factor b

RB:

Retinoblastoma

OSCC:

Oral squamous cell carcinoma

DEX:

Dexamethasone

MAPK:

Mitogen-activated protein kinase

Hh:

Hedgehog

YAP:

Yes-associated protein

CDPP:

Cisplatin

ADM:

Adriamycin

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.

    Article  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

    Article  PubMed  Google Scholar 

  3. Park J. Look KA. Health care expenditure burden of cancer care in the United States. NQUIRY J Health Care Org Provis Financing. 2019;56:0046958019880696.

    Google Scholar 

  4. Altice CK, Banegas MP, Tucker-Seeley RD, Yabroff KR. Financial hardships experienced by cancer survivors: a systematic review. J Natl Cancer Inst. 2017;109(2):djw205.

    Article  PubMed  Google Scholar 

  5. Grillone K, Riillo C, Scionti F, Rocca R, Tradigo G, Guzzi PH, et al. Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”. 2020;39(1):1–19.

  6. Zangouei AS, Rahimi HR, Mojarrad M, Moghbeli M. Non coding RNAs as the critical factors in chemo resistance of bladder tumor cells. Diagn Pathol. 2020;15(1):136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guttman M, Rinn JLJN. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Esteller MJ. Non-coding RNAs in human disease. Nat Genet Res. 2011;12(12):861–74.

    Article  CAS  Google Scholar 

  9. Vo JN, Zhang Y, Shukla S, Xiao L, Robinson D, Wu Y-M, et al. The landscape of circular RNA in cancer. Cell. 2018;176(4):869–8.

    Article  CAS  Google Scholar 

  10. Moreno-Moya JM, Vilella F, Simon C. MicroRNA: key gene expression regulators. Fertil Steril. 2014;101(6):1516–23.

    Article  CAS  PubMed  Google Scholar 

  11. Peláez N, Carthew RW. Biological robustness and the role of microRNAs: a network perspective. Curr Top Dev Biol. 2012;99:237–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13(4):271–82.

    Article  CAS  PubMed  Google Scholar 

  13. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28(3):369–78.

    Article  CAS  PubMed  Google Scholar 

  14. Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 2010;42(8):1273–81.

    Article  CAS  PubMed  Google Scholar 

  15. Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20(8):460–9.

    Article  CAS  PubMed  Google Scholar 

  16. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087–92.

    Article  CAS  PubMed  Google Scholar 

  17. Weber JA, Baxter DH, Zhang S, Huang DY, How Huang K, Jen Lee M, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gablo NA, Prochazka V, Kala Z, Slaby O, Kiss I. Cell-free microRNAs as non-invasive diagnostic and prognostic biomarkers in pancreatic cancer. Curr Genomics. 2019;20(8):569–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Imaoka H, Toiyama Y, Fujikawa H, Hiro J, Saigusa S, Tanaka K, et al. Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. Ann Oncol. 2016;27(10):1879–86.

    Article  CAS  PubMed  Google Scholar 

  20. Jin Y, Wong YS, Goh BK, Chan CY, Cheow PC, Chow PK, et al. Circulating microRNAs as potential diagnostic and prognostic biomarkers in hepatocellular carcinoma. Sci Rep. 2019;9(1):1–12.

    Google Scholar 

  21. Li H, Song F, Chen X, Li Y, Fan J, Wu X. Bmi-1 regulates epithelial-to-mesenchymal transition to promote migration and invasion of breast cancer cells. Int J Clin Exp Pathol. 2014;7(6):3057–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Nudelman AS, DiRocco DP, Lambert TJ, Garelick MG, Le J, Nathanson NM, et al. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus. 2010;20(4):492–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang ZG, Chen WX, Wu YH, Liang HF, Zhang BX. MiR-132 prohibits proliferation, invasion, migration, and metastasis in breast cancer by targeting HN1. Biochem Biophys Res Commun. 2014;454(1):109–14.

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Han J, Fan S, Yang W, Zhang Y, Xu T, et al. miR-132 weakens proliferation and invasion of glioma cells via the inhibition of Gli1. Eur Rev Med Pharmacol Sci. 2018;22(7):1971–8.

    PubMed  Google Scholar 

  25. Li Y, Zu L, Wang Y, Wang M, Chen P, Zhou Q. miR-132 inhibits lung cancer cell migration and invasion by targeting SOX4. J Thorac Dis. 2015;7(9):1563.

    PubMed  PubMed Central  Google Scholar 

  26. Zhao D, Hou Y, Sun F, Han B, Li SJ. Effects of miR-132 on proliferation and apoptosis of pancreatic cancer cells via Hedgehog signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(5):1978–85.

    PubMed  Google Scholar 

  27. Zhang H, Liu A, Feng X, Tian L, Bo W, Wang H, et al. MiR-132 promotes the proliferation, invasion and migration of human pancreatic carcinoma by inhibition of the tumor suppressor gene PTEN. Prog Biophys Mol Biol. 2019;148:65–72.

    Article  CAS  PubMed  Google Scholar 

  28. Aguda BD. Modeling microRNA-transcription factor networks in cancer. Adv Exp Med Biol. 2013;774:149–67.

    Article  CAS  PubMed  Google Scholar 

  29. Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27(16):2320–36.

    Article  CAS  PubMed  Google Scholar 

  30. Li W, Zhang J, Chen T, Yin P, Yang J, Cao Y. miR-132 upregulation promotes gastric cancer cell growth through suppression of FoxO1 translation. Tumour Biol. 2015. https://doi.org/10.1007/s13277-015-3924-y.

    Article  PubMed  Google Scholar 

  31. He K, Zeng H, Xu X, Li A, Cai Q, Long X. Clinicopathological significance of forkhead box protein A1 in breast cancer: a meta-analysis. Exp Ther Med. 2016;11(6):2525–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li YL, Zhao YG, Chen B, Li XF. MicroRNA-132 sensitizes nasopharyngeal carcinoma cells to cisplatin through regulation of forkhead box A1 protein. Pharmazie. 2016;71(12):715–8.

    CAS  PubMed  Google Scholar 

  33. Droog M, Nevedomskaya E, Kim Y, Severson T, Flach KD, Opdam M, et al. Comparative cistromics reveals genomic cross-talk between FOXA1 and ERalpha in tamoxifen-associated endometrial carcinomas. Can Res. 2016;76(13):3773–84.

    Article  CAS  Google Scholar 

  34. Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS. FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet. 2011;43(1):27–33.

    Article  CAS  PubMed  Google Scholar 

  35. Wang D, Ren J, Ren H, Fu JL, Yu D. MicroRNA-132 suppresses cell proliferation in human breast cancer by directly targeting FOXA1. Acta Pharmacol Sin. 2018;39(1):124–31.

    Article  CAS  PubMed  Google Scholar 

  36. Chen X, Li M, Zhou H, Zhang L. miR-132 targets FOXA1 and exerts tumor-suppressing functions in thyroid cancer. Oncol Res. 2019;27(4):431–7.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Cao LH, Li HT, Lin WQ, Tan HY, Xie L, Zhong ZJ, et al. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Sci Rep. 2016;6:18706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liang R, Han B, Li Q, Yuan Y, Li J, Sun D. Using RNA sequencing to identify putative competing endogenous RNAs (ceRNAs) potentially regulating fat metabolism in bovine liver. Sci Rep. 2017;7(1):6396.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Li Z, Han K, Zhang D, Chen J, Xu Z, Hou L. The role of long noncoding RNA in traumatic brain injury. Neuropsychiatr Dis Treat. 2019;15:1671–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pirogov SA, Gvozdev VA, Klenov MS. Long noncoding RNAs and stress response in the nucleolus. Cells. 2019;8(7):688.

    Article  CAS  Google Scholar 

  41. Rahmani Z, Mojarrad M, Moghbeli M. Long non-coding RNAs as the critical factors during tumor progressions among Iranian population: an overview. Cell Biosci. 2020;10:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Liu W, Tang J, Zhang H, Kong F, Zhu H, Li P, et al. A novel lncRNA PTTG3P/miR-132/212-3p/FoxM1 feedback loop facilitates tumorigenesis and metastasis of pancreatic cancer. Cell Death Discov. 2020;6(1):136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Xue MY, Cao HX. LINC01551 promotes metastasis of nasopharyngeal carcinoma through targeting microRNA-132-5p. Eur Rev Med Pharmacol Sci. 2020;24(7):3724–33.

    PubMed  Google Scholar 

  44. Hersh CP, Silverman EK, Gascon J, Bhattacharya S, Klanderman BJ, Litonjua AA, et al. SOX5 is a candidate gene for chronic obstructive pulmonary disease susceptibility and is necessary for lung development. Am J Respir Crit Care Med. 2011;183(11):1482–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Renjie W, Haiqian L. MiR-132, miR-15a and miR-16 synergistically inhibit pituitary tumor cell proliferation, invasion and migration by targeting Sox5. Cancer Lett. 2015;356(2 Pt B):568–78.

    Article  PubMed  CAS  Google Scholar 

  46. Wilusz JE, Sharp PA. Molecular biology. A circuitous route to noncoding RNA. Science. 2013;340(6131):440–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chen I, Chen CY, Chuang TJ. Biogenesis, identification, and function of exonic circular RNAs. Wiley Interdiscipl Rev RNA. 2015;6(5):563–79.

    Article  CAS  Google Scholar 

  48. Salzman J, Circular RNA. Expression: its potential regulation and function. Trends Genet. 2016;32(5):309–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liu P, Li X, Guo X, Chen J, Li C, Chen M, et al. Circular RNA DOCK1 promotes bladder carcinoma progression via modulating circDOCK1/hsa-miR-132–3p/Sox5 signalling pathway. Cell Prolif. 2019;52(4):e12614.

    PubMed  PubMed Central  Google Scholar 

  50. Gopal K, Gupta N, Zhang H, Alshareef A, Alqahtani H, Bigras G, et al. Oxidative stress induces the acquisition of cancer stem-like phenotype in breast cancer detectable by using a Sox2 regulatory region-2 (SRR2) reporter. Oncotarget. 2016;7(3):3111–27.

    Article  PubMed  Google Scholar 

  51. Zhou K, Zhang C, Yao H, Zhang X, Zhou Y, Che Y, et al. Knockdown of long non-coding RNA NEAT1 inhibits glioma cell migration and invasion via modulation of SOX2 targeted by miR-132. Mol Cancer. 2018;17(1):105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Abbaszadegan MR, Moghbeli M. Role of MAML1 and MEIS1 in esophageal squamous cell carcinoma depth of invasion. Pathol Oncol Res. 2018;24(2):245–50.

    Article  CAS  PubMed  Google Scholar 

  53. Moghbeli M, Mosannen Mozaffari H, Memar B, Forghanifard MM, Gholamin M, Abbaszadegan MR. Role of MAML1 in targeted therapy against the esophageal cancer stem cells. J Transl Med. 2019;17(1):126.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Moghbeli M, Rad A, Farshchian M, Taghehchian N, Gholamin M, Abbaszadegan MR. Correlation between Meis1 and Msi1 in esophageal squamous cell carcinoma. J Gastrointest Cancer. 2016;47(3):273–7.

    Article  CAS  PubMed  Google Scholar 

  55. Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci. 2003;116(Pt 3):499–511.

    Article  CAS  PubMed  Google Scholar 

  56. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83.

    Article  CAS  PubMed  Google Scholar 

  57. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117(7):927–39.

    Article  CAS  PubMed  Google Scholar 

  58. Liu Y, Li Y, Liu J, Wu Y, Zhu Q. MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4. Int J Oncol. 2015;47(5):1672–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wang L, Zhang J, Yang X, Chang YW, Qi M, Zhou Z, et al. SOX4 is associated with poor prognosis in prostate cancer and promotes epithelial-mesenchymal transition in vitro. Prostate Cancer Prostatic Dis. 2013;16(4):301–7.

    Article  CAS  PubMed  Google Scholar 

  60. Fu W, Tao T, Qi M, Wang L, Hu J, Li X, et al. MicroRNA-132/212 upregulation inhibits TGF-beta-mediated epithelial-mesenchymal transition of prostate cancer cells by targeting SOX4. Prostate. 2016;76(16):1560–70.

    Article  CAS  PubMed  Google Scholar 

  61. Li Y, Zu L, Wang Y, Wang M, Chen P, Zhou Q. miR-132 inhibits lung cancer cell migration and invasion by targeting SOX4. J Thorac Dis. 2015;7(9):1563–9.

    PubMed  PubMed Central  Google Scholar 

  62. Huang J, Lu D, Xiang T, Wu X, Ge S, Wang Y, et al. MicroRNA-132-3p regulates cell proliferation, apoptosis, migration and invasion of liver cancer by targeting Sox4. Oncol Lett. 2020;19(4):3173–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Chen HZ, Tsai SY, Leone G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer. 2009;9(11):785–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tian H, Hou L, Xiong YM, Huang JX, Zhang WH, Pan YY, et al. miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells. Am J Transl Res. 2016;8(3):1492–501.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Haigis MC, Guarente LP. Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20(21):2913–21.

    Article  CAS  PubMed  Google Scholar 

  66. Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell. 2006;126(2):257–68.

    Article  CAS  PubMed  Google Scholar 

  67. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004;86(11):839–48.

    Article  CAS  PubMed  Google Scholar 

  68. Li Y, Zhang J, He J, Zhou W, Xiang G, Xu R. MicroRNA-132 cause apoptosis of glioma cells through blockade of the SREBP-1c metabolic pathway related to SIRT1. Biomed Pharmacother. 2016;78:177–84.

    Article  CAS  PubMed  Google Scholar 

  69. He S, Deng Y, Liao Y, Li X, Liu J, Yao S. CREB5 promotes tumor cell invasion and correlates with poor prognosis in epithelial ovarian cancer. Oncol Lett. 2017;14(6):8156–61.

    PubMed  PubMed Central  Google Scholar 

  70. Zhang M, Li Y, Wang H, Yu W, Lin S, Guo J. LncRNA SNHG5 affects cell proliferation, metastasis and migration of colorectal cancer through regulating miR-132-3p/CREB5. Cancer Biol Ther. 2019;20(4):524–36.

    Article  CAS  PubMed  Google Scholar 

  71. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439(7078):871–4.

    Article  CAS  PubMed  Google Scholar 

  72. Cao R, Zhang Y. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev. 2004;14(2):155–64.

    Article  CAS  PubMed  Google Scholar 

  73. Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, et al. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 2013;23(6):768–83.

    Article  CAS  PubMed  Google Scholar 

  74. Lin L, Wang Z, Jin H, Shi H, Lu Z, Qi Z. MiR-212/132 is epigenetically downregulated by SOX4/EZH2-H3K27me3 feedback loop in ovarian cancer cells. Tumour Biol. 2016. https://doi.org/10.1007/s13277-016-5339-9.

    Article  PubMed  Google Scholar 

  75. Weng MY, Li L, Feng SY, Hong SJ. Expression of Bmi-1, P16, and CD44v6 in uterine cervical carcinoma and its clinical significance. Cancer Biol Med. 2012;9(1):48–53.

    PubMed  PubMed Central  Google Scholar 

  76. Liu YL, Jiang SX, Yang YM, Xu H, Liu JL, Wang XS. USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway. Cell Biochem Biophys. 2012;62(1):229–35.

    Article  CAS  PubMed  Google Scholar 

  77. Tong YQ, Liu B, Zheng HY, He YJ, Gu J, Li F, et al. Overexpression of BMI-1 is associated with poor prognosis in cervical cancer. Asia Pac J Clin Oncol. 2012;8(4):e55-62.

    Article  PubMed  Google Scholar 

  78. Liu GF, Zhang SH, Li XF, Cao LY, Fu ZZ, Yu SN. Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1. Oncotarget. 2017;8(46):80757–69.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Zhang XL, Sun BL, Tian SX, Li L, Zhao YC, Shi PP. MicroRNA-132 reverses cisplatin resistance and metastasis in ovarian cancer by the targeted regulation on Bmi-1. Eur Rev Med Pharmacol Sci. 2019;23(9):3635–44.

    PubMed  Google Scholar 

  80. Zhang K, Li Y, Qu L, Ma X, Zhao H, Tang Y. Long noncoding RNA Sox2 overlapping transcript (SOX2OT) promotes non-small-cell lung cancer migration and invasion via sponging microRNA 132 (miR-132). Onco Targets Ther. 2018;11:5269–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zheng YB, Luo HP, Shi Q, Hao ZN, Ding Y, Wang QS, et al. miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2. World J Gastroenterol. 2014;20(21):6515–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Murtaza M, Jolly LA, Gecz J, Wood SA. La FAM fatale: USP9X in development and disease. Cell Mol Life Sci. 2015;72(11):2075–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kushwaha D, O’Leary C, Cron KR, Deraska P, Zhu K, D’Andrea AD, et al. USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer cells expressing mid-to-high MCL1. Cancer Biol Ther. 2015;16(3):392–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Guo H, Zhang X, Chen Q, Bao Y, Dong C, Wang X. miR-132 suppresses the migration and invasion of lung cancer cells by blocking USP9X-induced epithelial-mesenchymal transition. Am J Transl Res. 2018;10(1):224–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Liu T, Liu J, Chen Q, Jin S, Mi S, Shao W, et al. Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma. Oncol Lett. 2019;17(2):2040–6.

    CAS  PubMed  Google Scholar 

  86. He X, Ma J, Zhang M, Cui J, Yang H. Long Non-Coding RNA SNHG16 Activates USP22 Expression to Promote Colorectal Cancer Progression by Sponging miR-132-3p. Onco Targets Ther. 2020;13:4283–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Varisli L, Ozturk BE, Akyuz GK, Korkmaz KS. HN1 negatively influences the beta-catenin/E-cadherin interaction, and contributes to migration in prostate cells. J Cell Biochem. 2015;116(1):170–8.

    Article  CAS  PubMed  Google Scholar 

  88. Liao J, He Q, Li M, Chen Y, Liu Y, Wang J. LncRNA MIAT: myocardial infarction associated and more. Gene. 2016;578(2):158–61.

    Article  CAS  PubMed  Google Scholar 

  89. Liu Z, Wang H, Cai H, Hong Y, Li Y, Su D, et al. Long non-coding RNA MIAT promotes growth and metastasis of colorectal cancer cells through regulation of miR-132/Derlin-1 pathway. Cancer Cell Int. 2018;18:59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Cheng ZX, Yin WB, Wang ZY. MicroRNA-132 induces temozolomide resistance and promotes the formation of cancer stem cell phenotypes by targeting tumor suppressor candidate 3 in glioblastoma. Int J Mol Med. 2017;40(5):1307–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liu X, Winey M. The MPS1 family of protein kinases. Annu Rev Biochem. 2012;81:561–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Liu X, Liao W, Yuan Q, Ou Y, Huang J. TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells. Oncotarget. 2015;6(33):34309–20.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Ritchie A, Gutierrez O, Fernandez-Luna JL. PAR bZIP-bik is a novel transcriptional pathway that mediates oxidative stress-induced apoptosis in fibroblasts. Cell Death Differ. 2009;16(6):838–46.

    Article  CAS  PubMed  Google Scholar 

  94. Chen S, Wang Y, Ni C, Meng G, Sheng X. HLF/miR-132/TTK axis regulates cell proliferation, metastasis and radiosensitivity of glioma cells. Biomed Pharmacother. 2016;83:898–904.

    Article  CAS  PubMed  Google Scholar 

  95. Kelly ML, Chernoff J. Getting smart about p21-activated kinases. Mol Cell Biol. 2011;31(3):386–7.

    Article  CAS  PubMed  Google Scholar 

  96. Liu F, Li X, Wang C, Cai X, Du Z, Xu H, et al. Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1. Int J Cancer. 2009;125(11):2511–9.

    Article  CAS  PubMed  Google Scholar 

  97. Kumar R, Sanawar R, Li X, Li F. Structure, biochemistry, and biology of PAK kinases. Gene. 2017;605:20–31.

    Article  CAS  PubMed  Google Scholar 

  98. Mazumdar A, Kumar R. Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells. FEBS Lett. 2003;535(1–3):6–10.

    Article  CAS  PubMed  Google Scholar 

  99. Xu J, Liu H, Chen L, Wang S, Zhou L, Yun X, et al. Hepatitis B virus X protein confers resistance of hepatoma cells to anoikis by up-regulating and activating p21-activated kinase 1. Gastroenterology. 2012;143(1):199–212.

    Article  CAS  PubMed  Google Scholar 

  100. Claps G, Cheli Y, Zhang T, Scortegagna M, Lau E, Kim H, et al. A transcriptionally inactive ATF2 variant drives melanomagenesis. Cell Rep. 2016;15(9):1884–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Van Obberghen-Schilling E, Tucker RP, Saupe F, Gasser I, Cseh B, Orend G. Fibronectin and tenascin-C: accomplices in vascular morphogenesis during development and tumor growth. Int J Dev Biol. 2011;55(4–5):511–25.

    Article  PubMed  CAS  Google Scholar 

  102. Liu F, Cheng Z, Li X, Li Y, Zhang H, Li J, et al. A novel Pak1/ATF2/miR-132 signaling axis is involved in the hematogenous metastasis of gastric cancer cells. Mol Ther Nucleic Acids. 2017;8:370–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Chung C. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics. J Oncol Pharm Pract. 2016;22(3):461–76.

    Article  CAS  PubMed  Google Scholar 

  104. Shabani M, Naseri J, Shokri F. Receptor tyrosine kinase-like orphan receptor 1: a novel target for cancer immunotherapy. Expert Opin Ther Targets. 2015;19(7):941–55.

    Article  CAS  PubMed  Google Scholar 

  105. Chauhan SC, Ebeling MC, Maher DM, Koch MD, Watanabe A, Aburatani H, et al. MUC13 mucin augments pancreatic tumorigenesis. Mol Cancer Ther. 2012;11(1):24–33.

    Article  CAS  PubMed  Google Scholar 

  106. Khan S, Ebeling MC, Zaman MS, Sikander M, Yallapu MM, Chauhan N, et al. MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. Oncotarget. 2014;5(17):7599–609.

    Article  PubMed  PubMed Central  Google Scholar 

  107. He L, Qu L, Wei L, Chen Y, Suo J. Reduction of miR1323p contributes to gastric cancer proliferation by targeting MUC13. Mol Med Rep. 2017;15(5):3055–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Qu W, Ding SM, Cao G, Wang SJ, Zheng XH, Li GH. miR-132 mediates a metabolic shift in prostate cancer cells by targeting Glut1. FEBS Open Bio. 2016;6(7):735–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Eramo A, Pallini R, Lotti F, Sette G, Patti M, Bartucci M, et al. Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction. Can Res. 2005;65(24):11469–77.

    Article  CAS  Google Scholar 

  110. Garofalo M, Romano G, Quintavalle C, Romano MF, Chiurazzi F, Zanca C, et al. Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis. Int J Cancer. 2007;120(6):1215–22.

    Article  CAS  PubMed  Google Scholar 

  111. Zanca C, Garofalo M, Quintavalle C, Romano G, Acunzo M, Ragno P, et al. PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer. J Cell Mol Med. 2008;12(6A):2416–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Geng F, Wu JL, Lu GF, Liang ZP, Duan ZL, Gu X. MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro. J Neurooncol. 2016;129(2):211–20.

    Article  CAS  PubMed  Google Scholar 

  113. Wang J, Xu G, Shen F, Kang Y. miR-132 targeting cyclin E1 suppresses cell proliferation in osteosarcoma cells. Tumour Biol. 2014;35(5):4859–65.

    Article  CAS  PubMed  Google Scholar 

  114. Peltier J, O’Neill A, Schaffer DV. PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation. Dev Neurobiol. 2007;67(10):1348–61.

    Article  CAS  PubMed  Google Scholar 

  115. Rafalski VA, Brunet A. Energy metabolism in adult neural stem cell fate. Prog Neurobiol. 2011;93(2):182–203.

    Article  CAS  PubMed  Google Scholar 

  116. Zhao X, Gan L, Pan H, Kan D, Majeski M, Adam SA, et al. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J. 2004;378(Pt 3):839–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Ho KK, Myatt SS, Lam EW. Many forks in the path: cycling with FoxO. Oncogene. 2008;27(16):2300–11.

    Article  CAS  PubMed  Google Scholar 

  118. Lam EW, Brosens JJ, Gomes AR, Koo CY. Forkhead box proteins: tuning forks for transcriptional harmony. Nat Rev Cancer. 2013;13(7):482–95.

    Article  CAS  PubMed  Google Scholar 

  119. Lian R, Lu B, Jiao L, Li S, Wang H, Miao W, et al. MiR-132 plays an oncogenic role in laryngeal squamous cell carcinoma by targeting FOXO1 and activating the PI3K/AKT pathway. Eur J Pharmacol. 2016;792:1–6.

    Article  CAS  PubMed  Google Scholar 

  120. Cai XM, Tao BB, Wang LY, Liang YL, Jin JW, Yang Y, et al. Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression. Int J Cancer. 2005;117(6):905–12.

    Article  CAS  PubMed  Google Scholar 

  121. Wu D, Li M, Tian W, Wang S, Cui L, Li H, et al. Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Sci Rep. 2017;7(1):5134.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Liu H, Pan Y, Han X, Liu J, Li R. MicroRNA-216a promotes the metastasis and epithelial-mesenchymal transition of ovarian cancer by suppressing the PTEN/AKT pathway. Onco Targets Ther. 2017;10:2701–9.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Zhang H, Liu A, Feng X, Tian L, Bo W, Wang H, et al. MiR-132 promotes the proliferation, invasion and migration of human pancreatic carcinoma by inhibition of the tumor suppressor gene PTEN. Prog Biophys Mol Biol. 2019;148:65–72.

    Article  CAS  PubMed  Google Scholar 

  124. Xie M, Fu Z, Cao J, Liu Y, Wu J, Li Q, et al. MicroRNA-132 and microRNA-212 mediate doxorubicin resistance by down-regulating the PTEN-AKT/NF-kappaB signaling pathway in breast cancer. Biomed Pharmacother. 2018;102:286–94.

    Article  CAS  PubMed  Google Scholar 

  125. Agami R. microRNAs, RNA binding proteins and cancer. Eur J Clin Invest. 2010;40(4):370–4.

    Article  CAS  PubMed  Google Scholar 

  126. Chen T, Lu M, Zhou X, Pan X, Han Y, Zhang Y, et al. miR-132 and miR-212 cluster function as a tumor suppressor in thyroid cancer cells by CSDE1 mediated post-transcriptional program. Int J Clin Exp Pathol. 2018;11(2):963–71.

    PubMed  PubMed Central  Google Scholar 

  127. Li L, Wei XH, Pan YP, Li HC, Yang H, He QH, et al. LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling. Oncogene. 2010;29(43):5785–95.

    Article  CAS  PubMed  Google Scholar 

  128. Li S, Xu JJ, Zhang QY. MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta in breast cancer. Cancer Sci. 2019;110(10):3098–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Zhang W, Liu Y, Fu Y, Han W, Xu H, Wen L, et al. Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3. Cancer Lett. 2020;478:22–33.

    Article  CAS  PubMed  Google Scholar 

  130. Zhao JL, Zhang L, Guo X, Wang JH, Zhou W, Liu M, et al. miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells. IUBMB Life. 2015;67(5):380–94.

    Article  CAS  PubMed  Google Scholar 

  131. Wei XC, Lv ZH. MicroRNA-132 inhibits migration, invasion and epithelial-mesenchymal transition via TGFbeta1/Smad2 signaling pathway in human bladder cancer. Onco Targets Ther. 2019;12:5937–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Han S, Song L, Chen Y, Hou M, Wei X, Fan D. The long non-coding RNA ILF3-AS1 increases the proliferation and invasion of retinoblastoma through the miR-132–3p/SMAD2 axis. Exp Cell Res. 2020;393(2):112087.

    Article  CAS  PubMed  Google Scholar 

  133. Chen L, Zhu Q, Lu L, Liu Y. MiR-132 inhibits migration and invasion and increases chemosensitivity of cisplatin-resistant oral squamous cell carcinoma cells via targeting TGF-beta1. Bioengineered. 2020;11(1):91–102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Pufall MA. Glucocorticoids and cancer. Adv Exp Med Biol. 2015;872:315–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Liu L, Aleksandrowicz E, Schonsiegel F, Groner D, Bauer N, Nwaeburu CC, et al. Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFbeta and JNK/AP-1. Cell Death Dis. 2017;8(10):e3064.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Abukiwan A, Nwaeburu CC, Bauer N, Zhao Z, Liu L, Gladkich J, et al. Dexamethasone-induced inhibition of miR-132 via methylation promotes TGF-beta-driven progression of pancreatic cancer. Int J Oncol. 2019;54(1):53–64.

    CAS  PubMed  Google Scholar 

  137. Guo YJ, Pan WW, Liu SB, Shen ZF, Xu Y, Hu LL. ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 2020;19(3):1997–2007.

    PubMed  PubMed Central  Google Scholar 

  138. Song XF, Chang H, Liang Q, Guo ZF, Wu JW. ZEB1 promotes prostate cancer proliferation and invasion through ERK1/2 signaling pathway. Eur Rev Med Pharmacol Sci. 2017;21(18):4032–8.

    PubMed  Google Scholar 

  139. Liu Y, Zhang M. miR-132 regulates adriamycin resistance in colorectal cancer cells through targeting extracellular signal-regulated kinase 1. Cancer Biother Radiopharm. 2019;34(6):398–404.

    Article  CAS  PubMed  Google Scholar 

  140. Song H, He P, Shao T, Li Y, Li J, Zhang Y. Long non-coding RNA XIST functions as an oncogene in human colorectal cancer by targeting miR-132-3p. J BUON. 2017;22(3):696–703.

    PubMed  Google Scholar 

  141. Bangs F, Anderson KV. Primary cilia and mammalian hedgehog signaling. Cold Spring Harb Perspect Biol. 2017;9(5):a028175.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Jung Y, McCall SJ, Li YX, Diehl AM. Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology. 2007;45(5):1091–6.

    Article  PubMed  Google Scholar 

  143. Zhao L, Yu Y, Deng C. Protein and mRNA expression of Shh, Smo and Gli1 and inhibition by cyclopamine in hepatocytes of rats with chronic fluorosis. Toxicol Lett. 2014;225(2):318–24.

    Article  CAS  PubMed  Google Scholar 

  144. Zhao DW, Hou YS, Sun FB, Han B, Li SJ. Effects of miR-132 on proliferation and apoptosis of pancreatic cancer cells via Hedgehog signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(5):1978–85.

    PubMed  Google Scholar 

  145. Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, et al. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol. 2007;17(23):2054–60.

    Article  CAS  PubMed  Google Scholar 

  146. Zhao B, Li L, Lei Q, Guan KL. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev. 2010;24(9):862–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Lei CJ, Li L, Gao X, Zhang J, Pan QY, Long HC, et al. Hsa-miR-132 inhibits proliferation of hepatic carcinoma cells by targeting YAP. Cell Biochem Funct. 2015;33(5):326–33.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Meysam Moghbeli & Zahra Nasrpour Navaii

  2. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Sadra Zangouei

  3. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Negin Taghehchian

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  1. Meysam Moghbeli
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  2. Amir Sadra Zangouei
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  3. Zahra Nasrpour Navaii
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  4. Negin Taghehchian
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ASZ, ZNN, and NT were involved in search strategy and drafting. MM supervised the project and revised and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Meysam Moghbeli.

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Moghbeli, M., Zangouei, A.S., Nasrpour Navaii, Z. et al. Molecular mechanisms of the microRNA-132 during tumor progressions. Cancer Cell Int 21, 439 (2021). https://doi.org/10.1186/s12935-021-02149-7

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  • DOI: https://doi.org/10.1186/s12935-021-02149-7

Keywords

  • MiR-132
  • Cancer
  • Diagnosis
  • Prognosis
  • Marker

Cancer Cell International

ISSN: 1475-2867

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