title: MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma.
abstract: MicroRNAs (miRNAs) have been found to play fundamental roles in the pathogenesis of hepatocellular carcinoma (HCC). Previous miRNA array data showed that miR-519a was upregulated in HCC tissues compared to adjacent non-tumor tissues. However, the functional role of miR-519a in HCC remains unexplored. In this study, we demonstrated that the expression of miR-519a was elevated in both HCC tissues and cell lines. Clinical association analysis revealed that high expression of miR-519a was correlated with adverse clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading, advanced tumor-node-metastasis (TNM) tumor stage and venous infiltration. Furthermore, high expression of miR-519a conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Moreover, we disclosed that miR-519a overexpression promoted, but miR-519a silencing reduced, HCC cell proliferation and cell cycle progression in vitro. Notably, we identified phosphatase and tensin homolog (PTEN) as a direct downstream target and functional mediator of miR-519a in HCC cells. Mechanistically, phosphatidylinositol-3-OH kinase (PI3K)/AKT pathway, downstream of PTEN, is essential for the functional roles of miR-519a in HCC cells. In conclusion, our results indicate that miR-519a promotes tumor growth of HCC by targeting PTEN-mediated PI3K/AKT pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Tu
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; C546194:MIRN519 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human