title: MicroRNA-34a targets Bcl-2 and sensitizes human hepatocellular carcinoma cells to sorafenib treatment.
abstract: MiR-34a, a direct target of p53, has been shown to target several molecules associated with the cell cycle and cell survival pathways, and its dysregulation is implicated in cancer drug resistance or sensitivity in several human cancers. However, the correlation between miR-34a expression and chemoresistance has not been explored in HCC. In this study, we confirmed that miR-34a was significantly down-regulated in HCC tissues and HCC cell lines by qRT-PCR. HCC tissues with lower miR-34a expression displayed higher expression of Bcl-2 protein than those with high expression of miR-34a; therefore, an inverse correlation is evident between the miR-34a level and Bcl-2 expression. Moreover, patients with lower miR-34a expression had significantly poorer overall survival. Bioinformatics and luciferase reporter assays revealed that miR-34a binds the 3'-UTR of the Bcl-2 mRNA and represses its translation. Western blotting analysis and qRT-PCR confirmed that Bcl-2 is inhibited by miR-34a overexpression. Functional analyses indicated that the restoration of miR-34a reduced cell viability, promoted cell apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell lines by inhibiting Bcl-2 expression. This study is the first to demonstrate that miR-34a induces sensitivity to the anti-tumor effect of sorafenib in human HCC cells, suggesting a potential role of miR-34a in the treatment of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, No. 17 Changle West Road, Xi'an, 710032, China. kefengdou126.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Qing-jun
authors.initials: QJ
authors.lastname: Li
authors.forename: Zhen-bin
authors.initials: ZB
authors.lastname: Gong
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Nan
authors.initials: N
authors.lastname: You
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Li
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Jia-ze
authors.initials: JZ
authors.lastname: An
authors.forename: De-sheng
authors.initials: DS
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Ke-feng
authors.initials: KF
authors.lastname: Dou
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D000077157:Sorafenib
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D010671:Phenylurea Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D009536:Niacinamide; D000077157:Sorafenib