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MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

  • Li, Ping (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Xie, Xiao-Bing (Medical Laboratory Center, First Affiliated Hospital, Hunan University of Chinese Medicine) ;
  • Chen, Qian (Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine) ;
  • Pang, Guo-Lian (Department of Pathology, First People Hospital of Qujing) ;
  • Luo, Wan (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Tu, Jian-Cheng (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Zheng, Fang (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Liu, Song-Mei (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Han, Lu (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University) ;
  • Zhang, Jian-Kun (Department of Pathology, First People Hospital of Qujing) ;
  • Luo, Xian-Yong (Department of Pathology, First People Hospital of Qujing) ;
  • Zhou, Xin (Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University)
  • Published : 2014.08.30

Abstract

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

Keywords

microRNA-15a;breast cancer;SNCG;cell cycle;apoptosis

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