Genome-wide screening identified that miR-134 acts as a metastasis suppressor by targeting integrin β1 in hepatocellular carcinoma.
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNAs that play pivotal roles in human cancer development and progression, such as tumor metastasis. Here, we identified the miRNAs that regulate hepatocellular carcinoma (HCC) cell migration by a high-throughput screening method using the classical wound-healing assay with time-lapse video microscopy and validation with a transwell migration assay. Eleven miRNAs (miR-134, -146b-3p, -188-3p, -525-3p, -661, -767-5p, -891a, -891b, -1244, -1247 and miR-1471) were found to promote or inhibit HCC cell migration. Further investigation revealed that miR-134 suppressed the invasion and metastasis of HCC cells in vitro and in vivo, and integrin beta 1 (ITGB1) was a direct and functional target gene of miR-134. Moreover, miR-134 inhibited the phosphorylation of focal adhesion kinase (FAK) and the activation of RhoA downstream of the ITGB1 pathway, thereby decreasing stress fiber formation and cell adhesion in HCC cells. In conclusion, we demonstrated that miR-134 is a novel metastasis suppressor in HCC and could be a potential therapeutic target for the treatment of HCC.
Shanghai Medical College, Fudan University, Shanghai, China ; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ruopeng
R
Zha
Shanghai Medical College, Fudan University, Shanghai, China ; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weijie
W
Guo
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenfeng
Z
Zhang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhaoping
Z
Qiu
Shanghai Cancer Hospital, Fudan University, Shanghai, China.
Qifeng
Q
Wang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jie
J
Ding
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shenglin
S
Huang
Qi Dong Liver Cancer Institute, Qi Dong, Jiangsu, China.
Taoyang
T
Chen
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianren
J
Gu
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ming
M
Yao
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xianghuo
X
He
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging / Q000379:methods; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D019012:Integrin beta1; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein