title: miR-145 regulates chemoresistance in hepatocellular carcinoma via epithelial mesenchymal transition.
abstract: Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular carcinoma (HCC) therapy. MicroRNA&mdash;145 (miR&mdash;145) has been shown to be down&mdash;regulated in several cancers and may be involved in the process of carcinogenesis. The present study aimed to evaluate the effects of miR&mdash;145 in adriamycin (ADM)&mdash;resistant human HCC cells. We found that miR&mdash;145 was significantly reduced in HepG2/ADM and HuH7/ADM cells compared with the chemosensitive parental cells. Up&mdash;regulation of miR&mdash;145 increased the ADM cytotoxicity in chemoresistant tumor cells. In addition, Smad3 was identi&#64257;ed as the target of miR&mdash;145 and miR&mdash;145 overexpression inhibited Smad3 expression both at the mRNA and protein levels. The luciferase reporter assay confirmed that Smad3 was a direct target of miR&mdash;145. Moreover, up&mdash;regulation of miR&mdash;145 suppressed Smad3 related EMT features as shown by increased expression of E&mdash;cadherin and reduced vimentin level in HepG2/ADM and HuH7/ADM cells. Our study demonstrated that miR&mdash;145 modulated both chemoresistance and EMT in HCC cells, and up&mdash;regulation of miR&mdash;145 might be a potential therapeutic strategy for treatment of chemoresistant HCC.
authors.affiliation: General Hospital of Beijing Command, PLA. Department of Hepatobilliary Surgery Beijing China.
authors.forename: B-L
authors.initials: BL
authors.lastname: Ju
authors.affiliation: General Hospital of Beijing Command, PLA. Department of Hepatobilliary Surgery Beijing China.
authors.forename: Y-B
authors.initials: YB
authors.lastname: Chen
authors.affiliation: General Hospital of Beijing Command, PLA. Department of Hepatobilliary Surgery Beijing China.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: General Hospital of Beijing Command, PLA. Department of Hepatobilliary Surgery Beijing China.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Shanghai Tongji Hospital, Tongji University Department of Pharmacy Shanghai China zdq_0726&commat;163.com.
authors.forename: D-Q
authors.initials: DQ
authors.lastname: Zhu
authors.affiliation: Shanghai Ninth People&apos;s Hospital Department of Pharmacy Shanghai China jinjjij&commat;126.com.
authors.forename: J
authors.initials: J
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D051900:Smad3 Protein; D014746:Vimentin; D004317:Doxorubicin