Li Ping, Xie Xiao-Bing, Chen Qian, Pang Guo-Lian, Luo Wan, Tu Jian-Cheng, Zheng Fang, Liu Song-Mei, Han Lu, Zhang Jian-Kun, Luo Xian-Yong, Zhou Xin
Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China E-mail :
Asian Pac J Cancer Prev. 2014;15(16):6949-54. doi: 10.7314/apjcp.2014.15.16.6949.
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-γ (SNCG).
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.
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.
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.
近期研究表明，微小RNA-15a（miR-15a）在乳腺癌（BC）中表达失调。我们旨在评估miR-15a在BC组织及相应癌旁组织中的表达情况。我们还关注了miR-15a对MDA-MB-231细胞行为及其靶基因突触核蛋白γ（SNCG）表达的影响。
通过微阵列和定量实时PCR分析BC福尔马林固定石蜡包埋（FFPE）组织中miR-15a的表达水平。采用CCK-8法、细胞周期和凋亡检测法探究miR-15a在人BC细胞MDA-MB-231中的潜在功能。荧光素酶报告基因检测确定直接靶点。
在大多数原发性BC中检测到miR-15a下调。miR-15a的异位表达在体内促进增殖并抑制凋亡。进一步研究表明，miR-15a可能直接与SNCG mRNA的3'非翻译区（3'-UTR）相互作用，下调其mRNA和蛋白表达水平。SNCG表达与miR-15a表达呈负相关。
MiR-15a在介导BC细胞周期阻滞和促进细胞凋亡中起关键作用，可能是通过直接靶向SNCG。因此，它可能参与BC的发生和发展。
