Skip to main content

Table 2 Summary of the role of miR-206 in malignant conditions (PTANTs: pairs of primary tumor tissues and adjacent normal tissues)

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]