title: miRNA-21 sensitizes gastrointestinal stromal tumors (GISTs) cells to Imatinib via targeting B-cell lymphoma 2 (Bcl-2).
abstract: miRNA-21 (miRNA-21) has recently been recognized to tumor suppressive in various types of cancers. However, the role of miRNA-21 in gastrointestinal stromal tumors (GISTs) is still ambiguous. In this study, we investigated the regulation by miRNA-21 on the sensitivity of gastrointestinal stromal tumors (GISTs) cells to Imatinib.
  
  
  
  We examined the expression of miRNA-21 and B-cell lymphoma 2 (Bcl-2) in GIST specimens by the real-time quantitative PCR assay (RT-qPCR). Then we explored the regulation by miRNA-21 on the Bcl-2 expression by the RT-qPCR assay, Western blotting assay and the luciferase assay in GIST-T1 cells. In addition, we examined the influence of miRNA-21 on the sensitivity to Imatinib of GIST-T1 cells with colony forming assay and apoptotic assay.
  
  
  
  Results indicated that miRNA-21 expression was suppressed in GIST tissues. And we identified putative miRNA-21 binding sites within the 3'-untranslated region (3'-UTR) of the human Bcl-2 gene. Transient transfection of miRNA-21 mimics into human GIST GIST-T1 cell line significantly downregulated the Bcl-2 expression in both mRNA and protein levels. Moreover, the miRNA-21 mimics transfection markedly aggravated the Imatinib-mediated growth inhibition and apoptosis induction in GIST-T1 cells.
  
  
  
  Our results demonstrated that miRNA-21 suppressed Bcl-2 expression in GIST cells and could function as a potent tumor suppressor in GIST. And the miRNA-21 promotion could sensitize GIST cells to Imatinib. It implies a potential role in the GIST treatment.
authors.affiliation: Department of Gastroenterology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. shironkang@sohu.com.
authors.forename: C-L
authors.initials: CL
authors.lastname: Cao
authors.forename: H-J
authors.initials: HJ
authors.lastname: Niu
authors.forename: S-P
authors.initials: SP
authors.lastname: Kang
authors.forename: C-L
authors.initials: CL
authors.lastname: Cong
authors.forename: S-R
authors.initials: SR
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D045744:Cell Line, Tumor; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell; D035683:MicroRNAs / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate