Skip to main content
Download PDF

MALAT1-related signaling pathways in colorectal cancer

Cancer Cell International volume 22, Article number: 126 (2022) Cite this article

Abstract

Colorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.

Introduction

Colorectal cancer (CRC) or colorectal adenocarcinoma is a complex and the third cause of malignancies in the world [1, 2]. CRC usually arises from the hyper-proliferative glandular and epithelial cells in the large intestine [3]. Several environmental and genetic factors can stimulate the accumulation of mutations and oncogenes, and inhibit tumor suppressor genes in colon epithelial cells [4]. Currently, surgical resection [5], chemotherapy [6], and radiotherapy [7] are the common types of treatments for CRC [8]. Recently, molecular targeted therapy has emerged as a novel treatment option for targeting CRC cells [9, 10]. Some studies provided evidence that cancer-specific long non-coding RNAs (lncRNAs) can be utilized for anti-CRC drugs [11, 12]. LncRNA (> 200 nucleotides in length) are transcribed RNA molecules that directly or indirectly regulate a variety of biological functions [13]. It has been shown that many lncRNAs are involved in human diseases and cancers through the induction of cell cycle progression, invasion, and metastasis [14]. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a conserved and well-characterized lncRNA that plays an important role in various biological processes through diverse mechanisms [15]. Under hypoxia conditions, MALAT1 plays an important role in inflammation, angiogenesis, and metastasis [16].

The expression of MALAT1 was first detected in patients with non-small cell lung cancer (NSCLC) [17, 18]. The expression of MALAT1 has been upregulated in multiple cancer types include liver [19], cervix [20], breast [21], colorectal [22], renal [23], prostate [24], gastric [25] and other cancers [26, 27]. In tumor cells, MALAT1 by targeting several transcription factors, growth factors, hormones, and epigenetic histone modifications can mediate cancer cell proliferation, tumorigenicity, autophagy, epithelial-mesenchymal transition (EMT), metastasis, and drug resistance phenotypes [28,29,30,31]. Recent studies elucidated the role of MALAT1 in CRC cell growth, migration, invasion, and metastasis [32, 33]. MALAT1 was reported to target several CRC-related pathways such as Wnt/β-catenin, YAP, SOX9, RUNX2, Snail, EGF, PI3K/AKT/mTOR, P53, and VEGF [34, 35]. Besides, MALAT1 by suppressing multiple microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis [36, 37]. miRNAs are epigenetic modulators that target mRNAs and function in various biological and pathological processes [38].

Therefore, MALAT1 can be a potent biomarker for CRC prediction and diagnosis [39, 40]. In this review, we summarized MALAT1-related signaling pathways in CRC.

Biogenesis of MALAT1

MALAT1 (known as nuclear-enriched abundant transcript 2 (NEAT2) or hepcarcin (HCN)) is the most widely investigated lncRNA and RNA polymerase II transcripts that localizes to nuclear speckles [41, 42]. MALAT1 coding gene is located on human chromosome 11q13.1 (> 8000 nucleotides) [28] and functions in alternative splicing [26]. The MALAT1 precursor contains a highly conserved triple-helix element at the 3′ end named MALAT1-associated small cytoplasmic RNA (mascRNA) that protects the 3′ end from degradation and facilitates the localization of MALAT1 [43, 44]. mascRNA with a tRNA-like structure is separated from MALAT precursor by tRNA endonucleases RNase P to generate pre-mature MALAT1 [45, 46]. RNase P can also generate a 61-nt tRNA-like small RNA at the 5’ end of the abundant MALAT1 transcript which is exported to the cytoplasm [47]. Pre-mature MALAT1 with a short poly(A) tail-like moiety is cleaved by tRNA endonucleases RNase Z in the nucleus, prior to addition of the CCA motif. After processing, mascRNA with CCA trinucleotide tail exported to the cytoplasm, while the stable MALAT1 transcript accumulates in the nucleus [48] (Fig. 1).

Fig. 1
figure 1

Characterization of MALAT1. MALAT1 contains a highly conserved triple-helix element at the 3′ end named MALAT1-associated small cytoplasmic RNA (mascRNA) that protects the 3′ end from degradation and facilitates the localization of MALAT1. mascRNA is a tRNA-like structure that is separated from MALAT precursor by tRNA endonucleases RNase P. Then, pre-mature MALAT1 with a short poly(A) tail-like moiety is cleaved by tRNA endonucleases RNase Z. MALAT1 plays functional roles in transcriptional regulation, translation activation, epigenetic regulation, RNA processing, physiological processes, and cancer

Full size image

MALAT1 interacts with multiple miRNAs and small nuclear RNAs (snRNAs) to regulate various biological processes in human tissues [46]. It has been reported that several nuclear speckles such as RNPS1 (RNA-binding protein with serine-rich domain 1), SRm160 (serine/arginine-rich (SR)-related protein), and IBP160 (intron binding protein) regulate the proper localization of MALAT1 to nuclear speckles [17]. MALAT1 also changes the distribution of SR splicing factor (SRSF), SON1, hnRNPC, and hnRNPH1 as pre-mRNA splicing factors [17, 49]. MALAT1 can target polycomb repressive complex 2 (PRC2) components (enhancer of Zeste 2 (EZH2), SUZ12, and EED), increase trimethylation of histone H3 at lysine 27 (H3K27me3), and decrease target gene or miRNA expression [50]. Down-regulation of MALAT1 influenced the distribution of SR proteins and changed splicing of pre-mRNA [51]. Nowadays, various specific gene manipulation methods using siRNAs, miRNAs, and shRNA mediated the knockdown of MALAT1 have been introduced for diagnostic, prognostic, and therapeutic values of MALAT1 and its downstream targets [17, 52]. Although the exact mechanism of MALAT1 is unclear, its expression is misregulated in numerous human malignancies. MALAT1 as a competing endogenous RNA (ceRNA) can sponge miRNAs to inhibit their expression and stimulate their downstream targets.

MALAT1 was suggested to be a prognostic marker in multiple cancerous tissues. Below, we summarized the overview function of MALAT1 in colorectal cancer.

The role of MALAT1 in colorectal cancer

The MALAT1 fragment at the 3' end is known to be associated with CRC cell metastasis [47, 53]. However, the exact mechanisms of MALAT1 in CRC are not fully understood. Previous studies have established that MALAT1 promotes CRC cell proliferation, apoptosis, migration, metastasis, and angiogenesis (Table 1). MALAT1 by targeting several signaling pathways and miRNAs plays a pivotal role in CRC pathogenesis (Fig. 2).

Table 1 MALAT1-related signaling pathways in colorectal cancer (CRC)
Full size table
Fig. 2
figure 2

MALAT1-related signaling pathways in CRC. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis

Full size image

Based on a previous study, MALAT1 as a prognostic risk factor decreased the survival outcomes of patients with CRC [54]. In advanced CRC patients, overexpression of MALAT1 is associated with drug resistance [22]. MALAT1 is able to increase oxymatrine resistance and the invasion ability of CRC cells [55]. MALAT1 by targeting at least 243 genes stimulates tumor development and enhances CRC cell invasion. The expression of PRKA kinase anchor protein 9 (AKAP-9) has been recognized that was increased in CRC tissues with lymph node metastasis [35].

A study reported that tumor-associated dendritic cells (TADCs) promoted migration and EMT in CRC [56]. C–C motif ligand 5 (CCL5) is a chemokine that mimics the impact of TADCs on CRC cells. Therefore, the inhibition of CCL5 expression via neutralizing antibodies or siRNA reduced cancer progression by TADCs. It has been suggested that Snail as the downstream target of MALAT1 participates in TADC-mediated CRC progression [56].

Further studies have found that MALAT1 can target miR‑619‑5p and increase the clinicopathological features of patients with CRC [57]. In CRC, MALAT1 through interaction with EZH2 can inhibit the expression of E-cadherin and induce Oxaliplatin (Ox) resistance. Also, MALAT1 interacts with miR-218 to enhance EMT, metastasis, and FOLFOX resistance [22]. MALAT1 by targeting miR-363-3p can enhance EZH2 expression levels and promote CRC cell proliferation [58].

PTBP2 or PTB (polypyrimidine-tract-binding protein) is a proto-oncogene that promotes the growth of CRC cells [59]. SFPQ or PSF is a PTB-associated splicing factor and a tumor suppressor gene that binds to PTBP2 [60]. MALAT1 has been observed that interacts with SFPQ, releases PTBP2 from the SFPQ/PTBP2 complex (SFPQ-detached PTBP2), and accelerates tumor growth and metastasis [61, 62].

Sex-determining region Y (SRY)-box 9 (SOX9) is a transcription factor that participates in CRC oncogenesis and metastasis [63]. MALAT1 by suppressing miR-145 could accelerate SOX9 mediated CRC cell proliferation, migration, and tumorigenesis (MALAT1/miR-145/SOX9 axis) [64].

MALAT1 has been proved that directly stimulates the expression of the mRNA‐decapping enzymes 1a (DCP1A), down-regulates miR-203, and enhances CRC cell proliferation and invasion (MALAT/miR-203/DCP1A axis) [65].

High mobility group box protein 1 (HMGB1) is a nuclear protein that enhances CRC cell development [66]. MALAT1 by targeting miR-129-5p increased the expression of HMGB1 (MALAT1/miR-129-5p/HMGB1 axis) and enhanced the proliferation of CRC cells [67].

Moreover, MALAT1 through the activation of Wnt/β-catenin signaling enhances CRC cell proliferation and reduces apoptosis (caspase-3 and Bax reduced, Bcl-2 increased) [68]. Resveratrol has been shown that down-regulates MALAT1 mediated the Wnt/β-catenin signal pathway and reduces CRC cell invasion and metastasis [69]. Therefore, the knockout of MALAT1 suppressed CRC cell migration and proliferation [54, 68].

MALAT1 by targeting key molecules participating in drug resistance, including breast cancer resistance protein (BCRP), ATP-binding cassette transporters (ABC), and multi-drug resistance proteins (MDR1 and MRP1) can increase the metastasis and invasion of CRC cells. Also, MALAT1 blocks the expression of miR-20b-5p and enhances CRC cell tumorigenesis. Hence, inhibition of MALAT1 reduced cell migration and promoted the sensitivity of CRC cells to 5-FU [70].

Yes-associated protein 1 (YAP1) has been reported that increases proliferation and migration of CRC cells [71]. YAP1 by targeting the MALAT1/miR-126-5p axis can stimulate vascular endothelial growth factor (VEGFA), SLUG, and TWIST as metastasis-associated molecules and control EMT and angiogenesis in CRC cells. miR-126-5p by blocking SLUG, TWIST, and VEGFA has a tumor suppressor role in CRC [72].

RUNX2 (Runt-related transcription factor 2) is a key transcription factor and proto-oncogene that plays an important role in various tumors. miR-15s by suppressing LRP6 expression (Wnt receptor) can block activation of β-catenin signaling. MALAT1 interacts with IRES domain in the 5′UTR of the RUNX2 mRNAs and increases translational levels of RUNX2. MALAT1 also via miR-15s/LRP6/β-catenin signaling positively regulates RUNX2 expression and enhances CRC cell metastasis [73].

MALAT1 was recently investigated that suppressed miR-194-5p and enhanced the migration and invasion of CRC cells [74]. In CRC tissues and cell lines, microtubule-associated protein 1A/1B-light chain 3 (LC3-II/I) reflects autophagosome formation [75]. There is a positive correlation between MALAT1 and LC3-II mRNA levels in CRC cells. MALAT1 by binding to miR-101 can stimulate CRC cell proliferation and LC3-II-induced autophagy, and suppress the expression of Sequestosome-1 (p62/SQSTM1) as an autophagosome cargo protein [76].

miR-101-3p was also reported to play as a tumor suppressor in various neoplasms [77]. A recent study confirmed that MALAT1 targeted miR-101-3p in radio-resistance cells and promoted CRC cell viability [78].

It has been found that high-dose Vitamin C administration has an inhibitory effect on MALAT1 and CRC metastasis [79].

A disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) is a protease for epidermal growth factor receptor (EGF-R) ligand processing [80]. It has been recently shown that ADAM17 can accelerate the tumorigenesis of CRC [81]. MALAT1 through suppression of miR-324-3p and stimulation of ADAM17 (as a target of miR-324-3p) could reduce the Ox-sensitivity of CRC cells in xenograft tumor mice treated with Ox [82]. Besides, MALAT1 was identified to inhibit the expression of the hsa-miR-194-5p and decrease the progression-free survival in patients with CRC [83].

RAB14 is a small GTPase member of the RAS oncogene family that enhances CRC cell proliferation [84]. MALAT1 as a ceRNA can target miR-508-5p and RAB14 (as a target of miR-508-5p) promote CRC progression [85].

Based on previous studies, endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) pathway is contributed to CRC metastasis [86, 87]. It has been found that the protein kinase R (PKR)‑like ER kinase (PERK), inositol‑requiring enzyme 1 (IRE1), and transcription factor 6 (ATF6) activate signaling pathways involved in the UPR [88]. ER stress by suppressing cyclin D1 (cell cycle machinery) and inducing apoptosis plays an important role in CRC metastasis [89]. Thapsigargin (TG) is an ER stress inducer that stimulates cell migration [90]. TG‑induced MALAT1 is associated with the expression of the PERK and IRE1 pathways. Moreover, in CRC tissue samples, MALAT1 is positively regulated with the X‑box‑binding protein 1 (XBP1) and ATF4 binding sites. Therefore, the IRE1/XBP1 and PERK/ATF4 signaling pathways are involved in MALAT1-induced CRC progression [91].

Exosomes also play critical roles in the progression of CRC [92, 93]. A previous study showed that highly metastatic CRC-derived exosomes could accelerate the fucosyltransferase 4 (FUT4) levels (a key enzyme of fucosylation), invasion, and metastasis in primary CRC cells. They indicated that MALAT1 by targeting miR-26a/26b promoted FUT4-associated fucosylation, stimulated the PI3K/AKT/mTOR pathway, and increased CRC cell proliferation and tumorigenesis (MALAT1/miR-26a/26b/FUT4 axis) [94].

A study identified that MALAT1 can interact with lincRNA-ROR, lncRNA-p21, p53 and increase the tumorigenesis of CRC cells [95].

The RNA-binding protein QUAKING (QK) is involved in apoptosis and the RNA stability of MALAT1. Recently, DANCR (lncRNA) was found to mediate the interaction between QK and MALAT1 (DANCR/QK/MALAT1 axis), increase the anti-apoptotic function of MALAT1, and reduce Doxorubicin (Dox)-induced apoptosis in CRC cells [96].

Therefore, compared to traditional methods, MALAT1 can be a novel biomarker for the early diagnosis and prognosis of CRC.

Conclusion

In this review, we highlighted the recently reported mechanism of MALAT1 in CRC. MALAT1 targets several signaling pathways such as Wnt/β-catenin, YAP, SOX9, RUNX2, Snail, EGF, PI3K/AKT/mTOR, and VEGF. Besides, MALAT1 has been found to modify miRNAs-associated drug sensitivity in CRC. Although these studies showed that MALAT1 plays a pivotal role in CRC tumorigenesis, the exact mechanisms whereby MALAT1 stimulates CRC development or invasion remains largely unclear. Taken together, the MALAT1-mediated treatment can be a critical therapeutic target for chemotherapy and radiotherapy sensitization.

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

ABC:

ATP-binding cassette transporters

ADAM17:

A disintegrin and metalloprotease metallopeptidase domain 17

AKAP-9:

PRKA kinase anchor protein 9

ATF6:

Transcription factor 6

BCRP:

Breast cancer resistance protein

CCL5:

C–C motif ligand 5

ceRNA:

Competing endogenous RNA

CRC:

Colorectal cancer

DCP1A:

Decapping enzymes 1a

EMT:

Epithelial-mesenchymal transition

ER:

Endoplasmic reticulum

EZH2:

Enhancer of Zeste 2

FUT4:

Fucosyltransferase 4

HCN:

Hepcarcin

HMGB1:

High mobility group box protein 1

H3K27me3:

Trimethylation of histone H3 at lysine 27

IBP160:

Intron binding protein

IRE1:

Inositol‑requiring enzyme 1

LC3-II/I:

Microtubule-associated protein 1A/1B-light chain 3

LncRNA:

Long non-coding RNAs

MALAT1:

Metastasis‐associated lung adenocarcinoma transcript‐1

mascRNA:

MALAT1-associated small cytoplasmic RNA

MDR:

Multi-drug resistance proteins

miRNAs:

MicroRNAs

NSCLC:

Non-small cell lung cancer

NEAT2:

Nuclear-enriched abundant transcript 2

Ox:

Oxaliplatin

PERK:

Protein kinase R (PKR)‑like ER kinase

PFS:

Progression-free survival

PRC2:

Polycomb repressive complex 2

PTB:

Polypyrimidine-tract-binding protein

RNPS1:

RNA-binding protein with serine-rich domain 1

RUNX2:

Runt-related transcription factor 2

SQSTM1:

Sequestosome-1

SRm160:

Serine/arginine-rich (SR)-related protein

SRSF:

SR splicing factor

TADCs:

Tumor-associated dendritic cells

UPR:

Unfolded protein response

VEGFA:

Vascular endothelial growth factor

YAP1:

Yes-associated protein 1

References

  1. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14:89–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sayhan S, Kahraman DS. Pathologic features of colorectal carcinomas. In: Colon polyps and colorectal cancer, Springer, 2020, pp. 455–480.

  3. Sekar V, Role of cancer stem cells in colitis-associated colorectal cancer, In: Diagnostic and treatment methods for ulcerative colitis and colitis-associated cancer, IGI Global, 2021, pp. 201–219.

  4. Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJH, Watanabe T. Colorectal cancer. Nat Rev Dis Primers. 2015;1:15065–15065.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Colov EP, Degett TH, Raskov H, Gögenur I. The impact of the gut microbiota on prognosis after surgery for colorectal cancer—a systematic review and meta-analysis. APMIS. 2020;128:162–76.

    Article  PubMed  Google Scholar 

  6. Mo X, Huang X, Feng Y, Wei C, Liu H, Ru H, Qin H, Lai H, Wu G, Xie W. Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients. OncoImmunology. 2020;9:1832347.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Häfner MF, Debus J. Radiotherapy for colorectal cancer: current standards and future perspectives. Visc Med. 2016;32:172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ghani S, Bahrami S, Rafiee B, Eyvazi S, Yarian F, Ahangarzadeh S, Khalili S, Shahzamani K, Jafarisani M, Bandehpour M, Kazemi B. Recent developments in antibody derivatives against colorectal cancer: a review. Life Sci. 2021;265:118791.

    Article  CAS  PubMed  Google Scholar 

  9. Barani M, Bilal M, Rahdar A, Arshad R, Kumar A, Hamishekar H, Kyzas GZ. Nanodiagnosis and nanotreatment of colorectal cancer: an overview. J Nanopart Res. 2021;23:1–25.

    Article  Google Scholar 

  10. Ali O, Tolaymat M, Hu S, Xie G, Raufman J-P. Overcoming obstacles to targeting muscarinic receptor signaling in colorectal cancer. Int J Mol Sci. 2021;22:716.

    Article  CAS  PubMed Central  Google Scholar 

  11. Yang Y, Yan X, Li X, Ma Y, Goel A. Long non-coding RNAs in colorectal cancer: novel oncogenic mechanisms and promising clinical applications. Cancer Lett. 2021;504:67–80.

    Article  CAS  PubMed  Google Scholar 

  12. Yang Y, Feng M, Bai L, Zhang M, Zhou K, Liao W, Lei W, Zhang N, Huang J, Li Q. The effects of autophagy-related genes and lncRNAs in therapy and prognosis of colorectal cancer. Front Oncol. 2021;11:582040.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fang Y, Fullwood MJ. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genomics Proteomics Bioinform. 2016;14:42–54.

    Article  Google Scholar 

  14. Do H, Kim W. Roles of oncogenic long non-coding RNAs in cancer development. Genomics Inform. 2018;16:e18–e18.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sun L, Zhang P, Lu W. lncRNA MALAT1 regulates mouse granulosa cell apoptosis and 17β-estradiol synthesis via regulating miR-205/CREB1 Axis. BioMed Res Int. 2021;2021:6671814.

    PubMed  PubMed Central  Google Scholar 

  16. Jiang X, Wang J, Deng X, Xiong F, Zhang S, Gong Z, Li X, Cao K, Deng H, He Y, Liao Q, Xiang B, Zhou M, Guo C, Zeng Z, Li G, Li X, Xiong W. The role of microenvironment in tumor angiogenesis. J Exp Clin Cancer Res. 2020;39:204.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Arun G, Aggarwal D, Spector DL. MALAT1 long non-coding RNA: functional implications. Non-coding RNA. 2020;6:22.

    Article  CAS  PubMed Central  Google Scholar 

  18. Wei Y, Niu B. Role of MALAT1 as a prognostic factor for survival in various cancers: a systematic review of the literature with meta-analysis. Dis Markers. 2015;2015:164635.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ji D-G, Guan L-Y, Luo X, Ma F, Yang B, Liu H-Y. Inhibition of MALAT1 sensitizes liver cancer cells to 5-flurouracil by regulating apoptosis through IKKα/NF-κB pathway. Biochem Biophys Res Commun. 2018;501:33–40.

    Article  CAS  PubMed  Google Scholar 

  20. Sun R, Qin C, Jiang B, Fang S, Pan X, Peng L, Liu Z, Li W, Li Y, Li G. Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition. Mol Biosyst. 2016;12:952–62.

    Article  CAS  PubMed  Google Scholar 

  21. Qiao F-H, Tu M, Liu H-Y. Role of MALAT1 in gynecological cancers: pathologic and therapeutic aspects. Oncol Lett. 2021;21:1–8.

    Article  Google Scholar 

  22. Li P, Zhang X, Wang H, Wang L, Liu T, Du L, Yang Y, Wang C. MALAT1 is associated with poor response to oxaliplatin-based chemotherapy in colorectal cancer patients and promotes chemoresistance through EZH2. Mol Cancer Ther. 2017;16:739–51.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang H, Li W, Gu W, Yan Y, Yao X, Zheng J. MALAT1 accelerates the development and progression of renal cell carcinoma by decreasing the expression of miR-203 and promoting the expression of BIRC5. Cell Prolif. 2019;52:e12640.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lu X, Chen D, Yang F, Xing N. Quercetin inhibits epithelial-to-mesenchymal transition (EMT) process and promotes apoptosis in prostate cancer via downregulating lncRNA MALAT1. Cancer Manag Res. 2020;12:1741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dai Q, Zhang T, Li C. LncRNA MALAT1 regulates the cell proliferation and cisplatin resistance in gastric cancer via PI3K/AKT pathway. Cancer Manag Res. 2020;12:1929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fu S, Wang Y, Li H, Chen L, Liu Q. Regulatory networks of LncRNA MALAT-1 in cancer. Cancer Manag Res. 2020;12:10181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li Q, Dai Y, Wang F, Hou S. Differentially expressed long non-coding RNAs and the prognostic potential in colorectal cancer. Neoplasma. 2016;63:977–83.

    Article  CAS  PubMed  Google Scholar 

  28. Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P, Tassone P. MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches. J Hematol Oncol. 2018;11:1–19.

    Article  Google Scholar 

  29. Amodio N, Raimondi L, Juli G, Stamato MA, Caracciolo D, Tagliaferri P, Tassone P. MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches. J Hematol Oncol. 2018;11:63–63.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhang X-Z, Liu H, Chen S-R. Mechanisms of long non-coding RNAs in cancers and their dynamic regulations. Cancers. 2020;12:1245.

    Article  CAS  PubMed Central  Google Scholar 

  31. Zhao K, Jin S, Wei B, Cao S, Xiong Z. Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer. Cancer Manag Res. 2018;10:6257–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen Q, Zhu C, Jin Y. The oncogenic and tumor suppressive functions of the long noncoding RNA MALAT1: an emerging controversy. Front Genet. 2020;11:93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Syllaios A, Moris D, Karachaliou GS, Sakellariou S, Karavokyros I, Gazouli M, Schizas D. Pathways and role of MALAT1 in esophageal and gastric cancer. Oncol Lett. 2021;21:1–7.

    Article  Google Scholar 

  34. Li Z-X, Zhu Q-N, Zhang H-B, Hu Y, Wang G, Zhu Y-S. MALAT1: a potential biomarker in cancer. Cancer Manag Res. 2018;10:6757–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yang MH, Hu ZY, Xu C, Xie LY, Wang XY, Chen SY, Li ZG. MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9. Biochim Biophys Acta. 2015;1852:166–74.

    Article  CAS  PubMed  Google Scholar 

  36. Wang L, Cho KB, Li Y, Tao G, Xie Z, Guo B. Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int J Mol Sci. 2019;20:5758.

    Article  CAS  PubMed Central  Google Scholar 

  37. Su K, Wang N, Shao Q, Liu H, Zhao B, Ma S. The role of a ceRNA regulatory network based on lncRNA MALAT1 site in cancer progression. Biomed Pharmacother. 2021;137:111389.

    Article  CAS  PubMed  Google Scholar 

  38. Farzaneh M, Alishahi M, Derakhshan Z, Sarani NH, Attari F, Khoshnam SE. The expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. Curr Stem Cell Res Ther. 2019;14:278–89.

    Article  CAS  PubMed  Google Scholar 

  39. Chen M, Wu D, Tu S, Yang C, Chen D, Xu Y. A novel biosensor for the ultrasensitive detection of the lncRNA biomarker MALAT1 in non-small cell lung cancer. Sci Rep. 2021;11:3666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, Sui H, Tang Y, Wang Y, Liu N. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer. 2014;111:736–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang X, Hamblin MH, Yin K-J. The long noncoding RNA Malat 1: its physiological and pathophysiological functions. RNA Biol. 2017;14:1705–14.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wilusz JE, Spector DL. An unexpected ending: noncanonical 3’ end processing mechanisms. RNA. 2010;16:259–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Donlic A, Zafferani M, Padroni G, Puri M, Hargrove AE. Regulation of MALAT1 triple helix stability and in vitro degradation by diphenylfurans. Nucleic Acids Res. 2020;48:7653–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Goyal B, Yadav SRM, Awasthee N, Gupta S, Kunnumakkara AB, Gupta SC. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875:188502.

    Article  CAS  PubMed  Google Scholar 

  45. Brown JA, Valenstein ML, Yario TA, Tycowski KT, Steitz JA. Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs. Proc Natl Acad Sci. 2012;109:19202–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. McCown PJ, Wang MC, Jaeger L, Brown JA. Secondary structural model of human MALAT1 reveals multiple structure–function relationships. Int J Mol Sci. 2019;20:5610.

    Article  CAS  PubMed Central  Google Scholar 

  47. Wilusz JE, Freier SM, Spector DL. 3’ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell. 2008;135:919–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Song Z, Lin J, Li Z, Huang C. The nuclear functions of long noncoding RNAs come into focus. Noncoding RNA Res. 2021;6:70–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yang F, Yi F, Han X, Du Q, Liang Z. MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett. 2013;587:3175–81.

    Article  CAS  PubMed  Google Scholar 

  50. Qu D, Sun W-W, Li L, Ma L, Sun L, Jin X, Li T, Hou W, Wang J-H. Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter. Nucleic Acids Res. 2019;47:3013–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lizarbe MA, Calle-Espinosa J, Fernández-Lizarbe E, Fernández-Lizarbe S, Robles MÁ, Olmo N, Turnay J. Colorectal cancer: from the genetic model to posttranscriptional regulation by noncoding RNAs. Biomed Res Int. 2017;2017:7354260.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Zhao M, Wang S, Li Q, Ji Q, Guo P, Liu X. MALAT1: a long non-coding RNA highly associated with human cancers. Oncol Lett. 2018;16:19–26.

    PubMed  PubMed Central  Google Scholar 

  53. Xu C, Yang M, Tian J, Wang X, Li Z. MALAT-1: a long non-coding RNA and its important 3’ end functional motif in colorectal cancer metastasis. Int J Oncol. 2011;39:169–75.

    PubMed  Google Scholar 

  54. Zheng H-T, Shi D-B, Wang Y-W, Li X-X, Xu Y, Tripathi P, Gu W-L, Cai G-X, Cai S-J. High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol. 2014;7:3174–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Xiong Y, Wang J, Zhu H, Liu L, Jiang Y. Chronic oxymatrine treatment induces resistance and epithelial-mesenchymal transition through targeting the long non-coding RNA MALAT1 in colorectal cancer cells. Oncol Rep. 2018;39:967–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kan J-Y, Wu D-C, Yu F-J, Wu C-Y, Ho Y-W, Chiu Y-J, Jian S-F, Hung J-Y, Wang J-Y, Kuo P-L. Chemokine (C-C Motif) ligand 5 is involved in tumor-associated dendritic cell-mediated colon cancer progression through non-coding RNA MALAT-1. J Cell Physiol. 2015;230:1883–94.

    Article  CAS  PubMed  Google Scholar 

  57. Qiu G, Zhang XB, Zhang SQ, Liu PL, Wu W, Zhang JY, Dai SR. Dysregulation of MALAT1 and miR-619-5p as a prognostic indicator in advanced colorectal carcinoma. Oncol Lett. 2016;12:5036–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Xie JJ, Li WH, Li X, Ye W, Shao CF. LncRNA MALAT1 promotes colorectal cancer development by sponging miR-363-3p to regulate EZH2 expression. J Biol Regul Homeost Agents. 2019;33:331–43.

    CAS  PubMed  Google Scholar 

  59. Hou P, Chen F, Yong H, Lin T, Li J, Pan Y, Jiang T, Li M, Chen Y, Song J, Zheng J, Bai J. PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α. J Exp Clin Cancer Res. 2019;38:301.

    Article  PubMed  PubMed Central  Google Scholar 

  60. He Q, Long J, Yin Y, Li Y, Lei X, Li Z, Zhu W. Emerging roles of lncRNAs in the formation and progression of colorectal cancer. Front Oncol. 2020;9:1542.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Amirkhah R, Naderi-Meshkin H, Shah JS, Dunne PD, Schmitz U. The intricate interplay between epigenetic events, alternative splicing and noncoding RNA deregulation in colorectal cancer. Cells. 2019;8:929.

    Article  CAS  PubMed Central  Google Scholar 

  62. Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, Sui H, Tang Y, Wang Y, Liu N, Ren J, Hou F, Li Q. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer. 2014;111:736–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Prévostel C, Blache P. The dose-dependent effect of SOX9 and its incidence in colorectal cancer. Eur J Cancer. 2017;86:150–7.

    Article  PubMed  Google Scholar 

  64. Xu Y, Zhang X, Hu X, Zhou W, Zhang P, Zhang J, Yang S, Liu Y. The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. Mol Med. 2018;24:52.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wu C, Zhu X, Tao K, Liu W, Ruan T, Wan W, Zhang C, Zhang W. MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation. Mol Carcinog. 2018;57:1421–31.

    Article  CAS  PubMed  Google Scholar 

  66. Süren D, Yıldırım M, Demirpençe Ö, Kaya V, Alikanoğlu AS, Bülbüller N, Yıldız M, Sezer C. The role of high mobility group box 1 (HMGB1) in colorectal cancer. Med Sci Monit. 2014;20:530–7.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Wu Q, Meng WY, Jie Y, Zhao H. LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis. J Cell Physiol. 2018;233:6750–7.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang J, Li Q, Xue B, He R. MALAT1 inhibits the Wnt/β-catenin signaling pathway in colon cancer cells and affects cell proliferation and apoptosis. Bosn J Basic Med Sci. 2020;20:357–64.

    PubMed  PubMed Central  Google Scholar 

  69. Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J, Li Q. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS ONE. 2013;8:e78700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tang D, Yang Z, Long F, Luo L, Yang B, Zhu R, Sang X, Cao G. Inhibition of MALAT1 reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer. Cell Signal. 2019;57:21–8.

    Article  CAS  PubMed  Google Scholar 

  71. Dehghanian F, Azhir Z, Akbari A, Hojati Z. New insights into the roles of yes-associated protein (YAP1) in colorectal cancer development and progression. Ann Colorectal Res. 2019;7:1–7.

    Article  Google Scholar 

  72. Sun Z, Ou C, Liu J, Chen C, Zhou Q, Yang S, Li G, Wang G, Song J, Li Z, Zhang Z, Yuan W, Li X. YAP1-induced MALAT1 promotes epithelial–mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer. Oncogene. 2019;38:2627–44.

    Article  CAS  PubMed  Google Scholar 

  73. Ji Q, Cai G, Liu X, Zhang Y, Wang Y, Zhou L, Sui H, Li Q. MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 in colorectal cancer metastasis. Cell Death Dis. 2019;10:378.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Wu S, Sun H, Wang Y, Yang X, Meng Q, Yang H, Zhu H, Tang W, Li X, Aschner M. MALAT1 rs664589 polymorphism inhibits binding to miR-194-5p, contributing to colorectal cancer risk, growth, and metastasis. Can Res. 2019;79:5432–41.

    Article  CAS  Google Scholar 

  75. Liu M, Zhao G, Zhang D, An W, Lai H, Li X, Cao S, Lin X. Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells. Int J Oncol. 2018;53:1363–73.

    CAS  PubMed  Google Scholar 

  76. Si Y, Yang Z, Ge Q, Yu L, Yao M, Sun X, Ren Z, Ding C. Long non-coding RNA Malat1 activated autophagy, hence promoting cell proliferation and inhibiting apoptosis by sponging miR-101 in colorectal cancer. Cell Mol Biol Lett. 2019;24:50.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Wang C-Z, Deng F, Li H, Wang D-D, Zhang W, Ding L, Tang J-H. MiR-101: a potential therapeutic target of cancers. Am J Transl Res. 2018;10:3310–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Guo J, Ding Y, Yang H, Guo H, Zhou X, Chen X. Aberrant expression of lncRNA MALAT1 modulates radioresistance in colorectal cancer in vitro via miR-101–3p sponging. Exp Mol Pathol. 2020;115:104448.

    Article  CAS  PubMed  Google Scholar 

  79. Chen J, Qin F, Li Y, Mo S, Deng K, Huang Y, Liang W. High-dose vitamin C tends to kill colorectal cancer with high MALAT1 expression. J Oncol. 2020;2020:2621308.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Soto-Gamez A, Chen D, Nabuurs AGE, Quax WJ, Demaria M, Boersma YL. A bispecific inhibitor of the EGFR/ADAM17 axis decreases cell proliferation and migration of EGFR-dependent cancer cells. Cancers. 2020;12:411.

    Article  CAS  PubMed Central  Google Scholar 

  81. Schumacher N, Rose-John S. ADAM17 activity and IL-6 trans-signaling in inflammation and cancer. Cancers. 2019;11:1736.

    Article  CAS  PubMed Central  Google Scholar 

  82. Fan C, Yuan Q, Liu G, Zhang Y, Yan M, Sun Q, Zhu C. Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells. Cancer Cell Int. 2020;20:1–12.

    Article  Google Scholar 

  83. Yang Q, Zheng W, Shen Z, Huang G, Yang G. MicroRNA binding site polymorphisms of the long-chain noncoding RNA MALAT1 are associated with risk and prognosis of colorectal cancer in Chinese Han population. Genet Test Mol Biomarkers. 2020;24:239–48.

    Article  CAS  PubMed  Google Scholar 

  84. Gopal Krishnan PD, Golden E, Woodward EA, Pavlos NJ, Blancafort P. Rab GTPases: emerging oncogenes and tumor suppressive regulators for the editing of survival pathways in cancer. Cancers. 2020;12:259.

    Article  PubMed Central  Google Scholar 

  85. Zhang C, Yao K, Zhang J, Wang C, Wang C, Qin C. Long noncoding RNA MALAT1 promotes colorectal cancer progression by acting as a ceRNA of miR-508-5p to regulate RAB14 expression. Biomed Res Int. 2020;2020:4157606.

    PubMed  PubMed Central  Google Scholar 

  86. Huang J, Pan H, Wang J, Wang T, Huo X, Ma Y, Lu Z, Sun B, Jiang H. Unfolded protein response in colorectal cancer. Cell Biosci. 2021;11:26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhao Q, Bi Y, Guo J, Liu Y, Zhong J, Liu Y, Pan L, Guo Y, Tan Y, Yu X. Effect of pristimerin on apoptosis through activation of ROS/endoplasmic reticulum (ER) stress-mediated noxa in colorectal cancer. Phytomedicine. 2021;80:153399.

    Article  CAS  PubMed  Google Scholar 

  88. Adams CJ, Kopp MC, Larburu N, Nowak PR, Ali MMU. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci. 2019;6:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Choi SS, Lee SK, Kim JK, Park H-K, Lee E, Jang J, Lee YH, Khim KW, Hyun J-M, Eom H-J, Lee S, Kang BH, Chae YC, Myung K, Myung S-J, Park CY, Choi JH. Flightless-1 inhibits ER stress-induced apoptosis in colorectal cancer cells by regulating Ca2+ homeostasis. Exp Mol Med. 2020;52:940–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Jaskulska A, Janecka AE, Gach-Janczak K. Thapsigargin—from traditional medicine to anticancer drug. Int J Mol Sci. 2021;22:4.

    Article  CAS  Google Scholar 

  91. Jiang X, Li D, Wang G, Liu J, Su X, Yu W, Wang Y, Zhai C, Liu Y, Zhao Z. Thapsigargin promotes colorectal cancer cell migration through upregulation of lncRNA MALAT1. Oncol Rep. 2020;43:1245–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Xiao Y, Zhong J, Zhong B, Huang J, Jiang L, Jiang Y, Yuan J, Sun J, Dai L, Yang C, Li Z, Wang J, Zhong T. Exosomes as potential sources of biomarkers in colorectal cancer. Cancer Lett. 2020;476:13–22.

    Article  CAS  PubMed  Google Scholar 

  93. Zhou J, Li X-L, Chen Z-R, Chng W-J. Tumor-derived exosomes in colorectal cancer progression and their clinical applications. Oncotarget. 2017;8:100781–90.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Xu J, Xiao Y, Liu B, Pan S, Liu Q, Shan Y, Li S, Qi Y, Huang Y, Jia L. Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway. J Exp Clin Cancer Res. 2020;39:1–15.

    Article  Google Scholar 

  95. Chaleshi V, Irani S, Alebouyeh M, Mirfakhraie R, Asadzadeh Aghdaei H. Association of lncRNA-p53 regulatory network (lincRNA-p21, lincRNA-ROR and MALAT1) and p53 with the clinicopathological features of colorectal primary lesions and tumors. Oncol Lett. 2020;19:3937–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Xiong M, Wu M, Dan P, Huang W, Chen Z, Ke H, Chen Z, Song W, Zhao Y, Xiang AP, Zhong X. LncRNA DANCR represses doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells. Cell Death Dis. 2021;12:24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Science Foundation of China (82074478 to RQL), the Project of six “1” Project of Jiangsu Province (LGY2016012 to XYW), Social Development Project of Jiangsu Province (BE2019768 to WXY), Maternal and Child Health Research Project of Jiangsu Province (F201763 to XWW) and Jiangsu Provincial Hospital of Traditional Chinese Medicine Research Fund Project (Y19053 to XWW). The funding institutions did not have any roles in the study design, data collection, or analysis.

Funding

Not applicable.

Author information

Author notes

  1. Wen-Wen Xu and Jin Jin are co-first authors

Authors and Affiliations

  1. Department of Gynaecology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing , 210029, Jiangsu, China

    Wen-Wen Xu, Jin Jin & Qing-Ling Ren

  2. Department of Surgical Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China

    Xiao-yu Wu

  3. Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Maryam Farzaneh

Authors
  1. Wen-Wen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-yu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing-Ling Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maryam Farzaneh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WX and JJ have been involved in drafting the manuscript. XW, QR, and MF have made substantial contributions to the revising of the manuscript and the design of the Figures. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiao-yu Wu or Qing-Ling Ren.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that there is no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, WW., Jin, J., Wu, Xy. et al. MALAT1-related signaling pathways in colorectal cancer. Cancer Cell Int 22, 126 (2022). https://doi.org/10.1186/s12935-022-02540-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12935-022-02540-y

Keywords

Cancer Cell International

ISSN: 1475-2867

Contact us