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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)
  • 발행 : 2014.08.30

초록

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.

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