title: Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma.
abstract: Aberrant expression of microRNAs has been identified as regulators of biological processes of hepatocellular carcinoma (HCC) by negatively regulating protein-coding mRNAs. Several studies have demonstrated that miR-638 expression was dysregulated in various human cancers. However, the clinical significance and underlying mechanisms of miR-638 involved in HCC remain to be elucidated. Herein, we confirmed that a reduced miR-638 expression was present in HCC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-638 expression was significantly correlated with poor prognostic features including high Edmondson-Steiner grade, venous infiltration and advanced tumor-node-metastasis (TNM) stage. Moreover, we demonstrated that miR-638 was a novel independent prognostic marker for predicting 5-year survival of HCC patients. Functionally, overexpressed miR-638 expression inhibited cell migration and invasion, while downregulated miR-638 reversed the effect. In addition, miR-638 could regulate SOX2 by directly binding to its 3'-UTR. Alternation of SOX2 expression at least partially abolished the migration and invasion effects of miR-638 on HCC cells. Aberrant miR-638 expression could regulate the expression level of epithelial-to-mesenchymal transition markers in vitro and in vivo by modulating SOX2 expression. In conclusion, our data indicated that miR-638 functioned as a tumor suppressor gene and play a critical role in the development of HCC.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C572154:MIRN638 microRNA, human; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors