title: miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway.
abstract: microRNAs (miRNAs) are key post-transcriptional regulators of gene expression in hepatocellular carcinoma (HCC), but their speciﬁc roles and functions have yet to be fully elucidated. In the present study, a significant downregulation of miR-139 expression was demonstrated in HCC samples and HCC cells using quantitative PCR (qPCR). Upregulation of miR-139 in vitro, attenuated HCC cell growth, migration/invasion and induced apoptosis. Based on computational and expression analysis, we noted that miR-139 can control the expression of T-cell factor-4 (TCF-4) as a target gene. A reporter assay with the 3'UTR of TCF-4 cloned downstream of a luciferase gene showed decreased luciferase activity in the presence of miR-139, providing strong evidence that miR-139 is a direct regulator of TCF-4. Furthermore, we observed that restoration of TCF-4 activity resulted in effects that were similar to those following transfection of the miR-139 inhibitor into HCC cells. Finally, mechanistic investigation revealed that the overexpression of miR-139 suppressed the β-catenin/TCF-4 transcriptional activity by targeting TCF-4. In conclusion, our study demonstrates that miR-139 downregulation is common in HCC and that overexpression of miR-139 expression inhibits cell proliferation and invasion, suggesting that miR-139 may provide a therapeutic strategy for the treatment of HCC patients.
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Li
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; C532096:TCF4 protein, human; C544894:TCF7L2 protein, human; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin