MicroRNA-129-5p inhibits hepatocellular carcinoma cell metastasis and invasion via targeting ETS1.
MiR-129-5p is deregulated in various human cancers and has been associated with hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of miR-129-5p involvement in the development and progression of HCC and the effects of miR-129-5p deregulation on the clinical characteristics observed in HCC patients remain poorly understood. We therefore investigated the correlation between low miR-129-5p expression and vascular invasion, intrahepatic metastasis, and poor patient survival. Ectopic restoration of miR-129-5p expression in HCC cells suppressed cellular migration and invasion and the expression of v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1), while inhibition of endogenous miR-129-5p caused an increase in these parameters. We identified the ETS1 gene as a novel direct target of miR-129-5p. SiRNA-mediated ETS1 knockdown rescued the effects of anti-miR-129-5p inhibitor in HCC cell lines, while the effects of miR-129-5p overexpression were partially phenocopied in the knockdown model. In addition, miR-129-5p levels inversely correlated with those of ETS1 in HCC cells and tissues. Taken together, our findings indicate an important role for miR-129-5p in the molecular etiology of invasive HCC and suggest that miR-129-5p could have potential therapeutic applications in HCC.
Department of Pancreato-Billary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Ning
N
Ma
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Fan
F
Chen
Department of Pancreato-Billary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Shun-Li
SL
Shen
Department of Pancreato-Billary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Wei
W
Chen
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Lian-Zhou
LZ
Chen
Animal Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Qiao
Q
Su
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Long-Juan
LJ
Zhang
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Jiong
J
Bi
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Wen-Tao
WT
Zeng
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Wen
W
Li
General Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: hxiaohui2006@126.com.
Xiao-Hui
XH
Huang
Department of Pancreato-Billary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: wangqian_dr@126.com.
Qian
Q
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D035683:MicroRNAs; C541915:Mirn129 microRNA, human
ETS1; Hepatocellular carcinoma; Invasion; miR-129-5p