From: Emerging roles and mechanisms of miR-206 in human disorders: a comprehensive review
Type of cancer | Expression Pattern | Samples | Animal studies/cell lines | Downstream targets | Pathway | Function | Kaplan–Meier | Refs. |
---|---|---|---|---|---|---|---|---|
Bladder Cancer (BC) | Down-regulation (transfected with RMRP promoter) | 20 serum specimens of BC patients | SV-HUC-1, BIU-87 and T24 | – | – | LncRNA RMRP acts as a miR-206 sponge and promotes proliferation, migratory aptitude and invasion in BC | – | [13] |
Breast cancer | Down-regulation | 59 PTANTs | MCF-7, T47D and SUM159 | PFKFB3 | Pentose phosphate pathway (PPP) | miR-206 reduces viability, proliferation and migration. miR-206 overexpression moderates glycolysis through PFKFB3 suppression | – | [14] |
Down-regulation | Breast cancer tissues and normal tissues | HEK293T, MCF-7 | CyclinD2 | – | miR-206 suppresses proliferation and colony formation through hindering G1/S transition. Downregulation of miR-206 is associated with larger tumor size and advanced clinical stage | – | [15] | |
Down-regulation (In estrogen receptor (ER) -positive compared with ERa-negative) | 94 breast tumor tissues | MCF-7 | – | – | miR-206 suppresses ERa expression and inhibits cell growth | – | [16] | |
Down-regulation | GEO-GSE 59,751 | MDA-MB-231, MCF-7, HS578t, and Hek293T Xenograft models | TWF1, IL11, MKL1 and SRF | MKL1/SRF | miR-206 inhibited cell cycle and self-renewal in tumorigenesis. It hampered cell motility | – | [17] | |
Down-regulation (in MCF-7 and MDA-MB-231 cell lines in compared with MCF-10A) | miRaNda algorithm, MiRmap and TargetScan | MCF-7, MDA-MB-231, MCF-10A and HEK-293 T | NAMPT | Nicotinamide Adenine Dinucleotide (NAD) | miR-206 suppresses cell survival and induced cell apoptosis through regulating NAMPT. Also, it plays a rule in breast cancer cell growth regulation | – | [20] | |
Down-regulation | – | MDA-MB-231 and MCF-7 | GATA-3, ER_, SRC-1, and SRC-3 | EGF/EGFR, EGFR/MAPK | miR-206 attenuates cell proliferation, induces apoptosis, and decreased expression of several estrogen-responsive genes by EGFR signaling | – | [21] | |
Down-regulation | – | MCF-7 and T47D | neuropilin-1 (NRP1), SMAD2, phospholipase D1 (PLD1) | TGF-β | Up-regulation of miR-206 prohibited migration and invasion of ER positive breast cancer cell lines. It also repressed EMT | – | [18] | |
Down-regulation | 15 paclitaxel-sensitive patients and 15 paclitaxel-resistant patients | MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453 and MCF-10 male BALB/c nude mice | FTH1P3, ABCB1 | FTH1P3/miR-206/ABCB1 | miR‐206 sponged by FTH1P3 in paclitaxel‐resistant patients and provided a novel insight in breast cancer chemoresistance | – | [22] | |
Up-regulation | 82 breast tumor tissues and their adjacent normal tissues | MCF10A, MDA-MB-231, SK-BR-3 Female BALB/c-nu mice | NK1R-FL, Erk1/2 | Phosphatidylinositol pathway, MAPK | miR-206 promotes invasion, proliferation, colony formation and migration in human breast cancer cells | – | [23] | |
Cervical cancer | Down-regulation | 41 PTANTs | – | Bcl2 and c-Met | – | Down-regulation of miR-206 induced advanced stage, advanced histological grade, metastasis and shorter survival in cervical cancer | Shorter overall survival | [19] |
Down-regulation | 35 PTANTs | Ect1/E6E7, Caski, C33A, SiHa and HeLa | GREM1 | Circ_0007534/miR-206/GREM1 | miR-206 inhibited the progression of cervical cancer by downregulation of GREM1 | – | [24] | |
Down-regulation | 50 cervical cancer tumor tissues | SiHa, HeLa and Normal human endocervical epithelial cells (NEECs) | BAG3, EGFR, MMP2, and MMP9 | miR-206–BAG3 | miR-206 suppresses proliferation, migration, and invasion | – | [25] | |
Down-regulation | – | HeLa, mouse | Notch3 | Notch3 | miR-206 acts as a tumor suppressor and activates cell death | – | [26] | |
Colon cancer | Up-regulation | – | HCT116, HT29, Caco2, SW48, SW480 and CCD841 Male F344 rats | Klf4 | – | Up-regulation of miR-206 plays a key role in etiology of cancers via targeting KLF4 and other pluripotency and cancer stem-cell factors. It also increased cell proliferation kinetics in colon cancer cell lines | – | [27] |
Colorectal Cancer (CRC) | Down-regulation (in 5-FU-resistant cells) | – | HCT116 and RKO | Bcl-2 | – | miR-206 regulated chemoresistance, proliferation, and apoptosis in CRC by targeting Bcl-2 | – | [28] |
Endometrial Cancer (EC) | Down-regulation | 36 EC patients and 8 patients with dysfunctional uterine bleeding and normal curettage | AN3C, RL95 and HEC-1-A | HDAC6 | PTEN/AKT/mTOR | miR-206 suppresses the proliferation, migration and invasion of endometrial cancer cells, via the PTEN/AKT/mTOR pathway | Poorer survival probability by targeting HDAC6 | [29] |
Endometrioid adenocarcinoma (EEC) | Down-regulation (in ERa-positive EECs) | 30 fresh-frozen EEC tissue samples | RL95-2, Ishikawa and KLE | CyclinD1 | MAPK | Expression of the tumor suppressor miR-206 is associated with inhibition of cell proliferation and reduces invasion in ERa-positive endometrioid adenocarcinoma | - | [30] |
Epithelial Ovarian Cancer (EOC) | Down-regulation | 50 EOC tissues and 20 normal tissues | SKOV3, HO8910, A2780, OVCAR, and HOSEpiC | c-Met | AKT/mTOR | miR-206 suppresses tumor cell growth, cell invasion and migration in EOC and down-regulation of miR-206 induced human EOC progression | Poor survival after surgery | [31] |
Up-regulation (in primary platinum-resistant EOCs) | 56 EOC patients | OV2008, A2780, Twenty female SCID mice | Connexin43 (Cx43) | – | Up-regulation of miR-206 enhanced cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis in cisplatin-sensitive EOC cell lines | Shorter overall survival | [32] | |
Esophageal Squamous Cell Carcinoma (ESCC) | Down-regulation | 30 PTANTs | ECA109, TE-1, KYSE150, KYSE-410 and HET-1A | NETO2 and FOXP1 | – | FAM225A increased NETO2 and FOXP1 levels by sponging miR-206 to advanced ESCC progression and angiogenesis | Shorter overall survival with a high level of FAM225A | [33] |
Gallbladder Cancer (GBC) | Down-regulation | 30 PTANTs | H69, NOZ, EH-GB1 GBC-SD and SGC-996 | ANXA2 and KRAS | – | miR-206 inhibits ANXA2 and KRAS expression, which increase GBC progression | – | [34] |
Gastric Cancer (GC) | Down-regulation | 30 PTANTs | SGC-7901, MKN-28, MKN-45 and GES-1 | CyclinD2 (CCND2) | – | miR-206 suppresses tumor cell growth, proliferation and induces cell cycle arrest at G0/G1 phase | – | [35] |
Hepatocellular Carcinoma (HCC) | Down-regulation | – | HepG2, Bell740, HLE and L02 | Cyclin-dependent kinase (CDK9) and Mcl-1 | miR-206/CDK9 | miR-206 suppresses tumor cell growth and proliferation by targeting CDK9 | – | [36] |
Laryngeal Squamous Cell Carcinoma (LSCC) | Down-regulation | 35 LSCC patients | Hep-2, BALB/c mice | VEGF | VEGF | Downregulation of miR-206 increases the proliferation and invasion of LSCC | Poor survival | [37] |
Down-regulation | 50 PTANTs | Hep-2, BALB/c nude mice(n = 12) | cyclinD2 | – | miR-206 inhibited the growth and tumorigenicity of LSCC cells via repressing cyclin D2 expression | – | [38] | |
Down-regulation | 311 LSCC and adjacent non‐tumorous tissues | TU-212 cells, AMC-HN-8 cells and HEK-293 T, BALB/c nude mice (n = 18) | DNMT3A | – | RP11-159K7.2 sponged miR-206 and thus, increased LSCC cell proliferation and invasion | Poorer overall survival in low expression of miR-206 | [39] | |
Liver Cancer | Down-regulation | HCC patients’ tissue samples | HL7702 (L02), Huh7, HepG2, Hep3B, CSQT-2, PLC and HCCLM3 | EGFR | EGFR | miR-206 suppressed the expansion of liver cancer stem cells via regulating EGFR | – | [40] |
Lung Cancer | Down-regulation (in high-metastatic strain) | 35 patients (20 adenocarcinoma patients, 15 squamous carcinoma patients) | 95D, 95C, A549, 801D, male BALB/c nude mice(n = 10) | MET | – | miR-206 inhibited cell migration, invasion and metastasis | – | [41] |
Down-regulation | – | PC-9, HCC827, male BALB/c nude mice(n = 9) | EGFR, c-Met | c-Met-Akt/Erk and Erk1/2 | miR-206 can restore HGF-induced gefitinib resistance in EGFR activated lung cancer cells by inhibition of Akt/Erk pathways and EMT | – | [42] | |
Nasopharyngeal carcinoma (NPC) | Down-regulation (in CNE2-IR compared with CNE2 cells) | – | CNE2, CNE2-IR | IGF1 | PI3K/AKT | miR-206 intenerates NPC cell to irradiation through targeting IGF1 | – | [43] |
Non-small cell lung cancer (NSCLC) | Down-regulation (in gefitinib-resistant NSCLC tumor tissues) | 78 lung cancer tissues (Gefitinib resistant (n = 36) and Gefitinib-sensitive (n = 42)) | PC9, Gefitinib-resistant PC9 (PC9/GR), Female BALB/C nude mice (n = 12) | ABCB1 | SNHG14-miR-206-3p-ABCB1 | miR-206-3p contribute to the chemoresistance of NSCLC to gefitinib via increasing ABCB1 | – | [44] |
Ovarian cancer | Down-regulation | 108 human ovarian cancer tissue samples | A2780, SKOV3 | KIF2A | – | Up-regulation of miR-206 enhanced apoptosis and inhibited proliferation, migration and invasion via decreasing KIF2A | – | [45] |
Down-regulation | 35 ovarian cancer cases and 17 normal cases | SKOV3, ES2 and OVCAR3, Female BALB/c nude mice (n = 10) | TBX3 | – | HOTAIR increases TBX3 expression via targeting miR-206, and promoting ovarian cancer stem cells | – | [46] | |
Papillary thyroid cancer (PTC) | Down-regulation | 23 patients with PTC | Nthy-ori3-1, TPC-1, TPC-1/euthyrox | MAP4K3 | MAPK, p38 and JNK | Up-regulation of miR-206 attenuated chemoresistance of drug-resistant PTC cells | – | [47] |
Up-regulation (in-baicalein treated patients) | – | TPC-1 | RAP1B | miR-206/RAP1B | miR-206 is involved in baicalein inhibition of PTC cell growth by regulating miR-206/RAP1B pathway | – | [48] | |
Prostate cancer (PCa) | Down-regulation | 35 patients with prostate cancer | 22RV1, DU145, PC3, and 293 T, female BALB/c nude mice (n = 24) | ubiquitin-specific peptidase 33 (USP33) | – | circ_0057558 sponged miR-206 and increased cell proliferation and cell cycle transition in prostate cancer cell lines | Longer overall survival | [49] |
Down-regulation | 10 pairs of PCa with adjacent control tissues | PC-3, DU-145, LNCaP and RWPE-1 | CXCL11 | – | miR-206 suppressed proliferation, tumor growth and activated cellular migration and invasion | – | [50] | |
Renal cell cancer (RCC) | Down-regulation | 42 RCC specimens | 786-O, OS-RC-2, and HK-2 | G-associated kinase (GAK) | – | miR-206 acts as a tumor suppressor through targeting GAK | – | [51] |
Down-regulation | 18 clear cell renal cell carcinoma (ccRCC) and 8 patients with benign renal tumors (BRT) and validation cohort (68 ccRCC, 47 BRT, and 28 healthy cases) | – | CDK4, CDK9, and CCND1 | – | Up-regulation of miR-206 inhibited cell proliferation and colony formation | Shorter overall survival and progression-free survival | [52] | |
Rhabdomyosarcoma (RMS) | Up-regulation | 10 patients with RMS, 28 patients with other pediatric tumors and 17 healthy cases | Rh30, SCMC-RM2, RD RMS-YM, CT-TC, Rh18 and Rh41, IMR32, GOTO, SK-N-SH, KP-N-RT, KP-EWS-YI, KPEWS-AK and KP-EWS-G401 and MRT-YM | – | – | miR-206 has the highest specificity and sensitivity among muscle-specific miRNAs, so it is the best biomarker for RMS prediction | – | [53] |
Head and neck squamous cell carcinoma (HNSCC) | Down-regulation | 22 pairs of primary tumors and normal epithelial samples, and 23 formalin-fixed paraffin-embedded tissues | FaDu, SAS and HSC3 | EGFR, c-MET, AKT and ERK1/2 | MAPK, Actin cytoskeleton and ECM–receptor, focal adhesion | Downregulation of miR-206 induced cancer cell aggressiveness via targeting EGFR and c-MET in HNSCC cells | – | [54] |
Thyroid cancer (TC) | Down-regulation | 60 tumor samples and matched noncancerous specimens | 8505C,TPC-1, SW1736, SW579 and Nthy-ori 3–1, female NOD/SCID mice (n = 10) | RAP1B | protein kinase A (PKA) | miR-206 inhibited cell activities of proliferation, invasion, and migration in TC via suppressing RAP1B expression | – | [55] |
Triple-negative breast cancer (TNBC) | Down-regulation | – | MDA-MB-231 and MDA-MB-436 Female athymic (nu/nu) BALB/c mice | Connexin43 (Cx43) | – | miR-206 represses the proliferation and invasion of TNBCs | [56] | |
Down-regulation | 83 TNBC tissues and 124 normal breast tissue samples | MCF-10A, MDA-MB-231, MDA-MB-468, SK-BR-3 and MCF-7, TNBC-bearing mice | – | PI3K/AKT/mTOR | miR-206 inhibited proliferation, migration, invasion, chemo-sensitivity and autophagy of TNBC cells | Poor 3-years survival | [57] | |
Down-regulation | 24 primary tumors and 13 normal breast tissue samples | MDA-MB-231, SUM159, MCF-10A, MCF-7 and T47D Mouse HC11 | CORO1C, TMSB4X, TPM4, and TNS3 | – | miR-206 reduced proliferation and migration in TNBC patients | [58] |