title: miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN.
abstract: MicroRNA-494 (miR-494) acts as an oncomiR and is involved in tumor development, progression and metastasis, and confers resistance to chemotherapeutic drugs by targeting a number of molecules in several human cancers. However, the function and underlying molecular mechanism of miR-494 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we determined the role played by miR-494 in HCC tissues and HCC cell lines using quantitative RT-PCR (RT-qPCR). The results showed that, miR-494 was significantly upregulated in HCC tissues and HCC cell lines. Additionally, a high miR-494 expression positively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Luciferase reporter assays confirmed that miR-494 binds to the 3'-untranslated region (3'-UTR) of the phosphatase and tensin homolog (PTEN) mRNA and represses its translation. Functional analyses indicated that the upregulation of miR-494 promoted cell viability, migration and invasion, decreased cell apoptosis and cell cycle arrest at G1 stage, and conferred sorafenib resistance to HCC cell lines. Underexpression of PTEN by siRNA significantly attenuated the inhibitory effects of anti-miR-494 on the proliferation, migration and invasion of liver cancer cells. Mechanistic investigations revealed that miR-494 suppressed the expression of PTEN but increased the expression of PI3K and p-Akt, which contribute to the promotion of proliferation, migration and invasion, and increased sorafenib resistance to HCC cell lines. These findings suggested that miR-494 is a potential candidate for HCC therapeutics.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Baoxing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Ludong
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009536:Niacinamide / Q000031:analogs & derivatives; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010671:Phenylurea Compounds; D011401:Promoter Regions, Genetic; D000077157:Sorafenib
chemical_list: C547168:MIRN494 microRNA, human; D035683:MicroRNAs; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human