title: MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4.
abstract: MicroRNAs (miRNAs) play a crucial role in cancer development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor prognostic factor for HCC patient overall and disease-free survival rate. A significant correlation was observed between miR-194 reduction and unfavourable variables including tumor size (P = 0.0315), histologic grade (P = 0.0038), TNM stage (P = 0.0083), intrahepatic metastasis (P = 0.0184). Overexpression of miR-194 in HCC cell lines HepG2 and Hep3B inhibited cell proliferation by blocking G1-S transition and inducing apoptosis. Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines. Further studies demonstrated that miR-194 regulated the progression of HCC through directly inhibiting the expression of MAP4K4 and the restoration of MAP4K4 expression reversed the inhibitory effects of miR-194 on HCC cell proliferation. Together, our findings indicate that miR-194 may serve as a valuable prognostic marker and promising interventional therapeutic target for HCC.
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Fenbao
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Aiguang
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Intervention, The First Hospital Affiliated to The Xinxiang Medical College Xinxiang, Henan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: MAP4K4; hepatocellular carcinoma; interventional therapy; microRNA-194; proliferation