title: MiR-138 Suppresses Cell Proliferation by Targeting Bag-1 in Gallbladder Carcinoma.
abstract: BACKGROUND
  MiR-138 is frequently downregulated in different cancer types and is thought to be involved in the progression of tumorigenesis. However, the molecular mechanism of miR-138 involvement in gallbladder carcinoma still remains unknown.
  
  
  METHODS
  The expression of miR-138 in 49 gallbladder carcinoma samples and paired normal gallbladder samples was analyzed using quantitative reverse transcription-polymerase chain reaction. The biological functions of miR-138 and Bag-1 (Bcl-2-associated athanogene-1) on cell proliferation were examined using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and apoptosis assays. Targets of miR-138 were predicted using bioinformatics and validated using luciferase reporter and Western blot analyses. The in vivo effects of miR-138 were examined using subcutaneous inoculation of gallbladder carcinoma cells in Balb/c nude mice.
  
  
  RESULTS
  Compared with their paired normal gallbladder samples, the gallbladder carcinoma samples had decreased expression of miR-138 and increased expression of Bag-1. Overexpression of miR-138 inhibited the proliferation of gallbladder carcinoma cells. Bag-1 was defined as a novel target of miR-138. Both the inhibition of Bag-1 by miR-138 and the silencing of Bag-1 by siRNA led to alterations of apoptosis-related proteins such as Bcl-2 and Bax. Restoring expression of Bag-1 eliminates the effects of miR-138 on cell proliferation and apoptosis. Furthermore, overexpression of miR-138 markedly inhibited the growth of tumors in the gallbladder carcinoma xenograft model in nude mice.
  
  
  CONCLUSIONS
  Expression of miR-138 is frequently reduced in gallbladder carcinoma when compared to normal cells. Overexpression of miR-138 inhibited cell proliferation by directly suppressing the expression of Bag-1. These results suggest that miR-138 plays an important role in inhibiting the growth of gallbladder carcinoma.
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Mingdi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Weng
authors.affiliation: Department of Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Quan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D020413:3' Untranslated Regions; C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors