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微小RNA-15a通过靶向突触核蛋白-γ介导乳腺癌细胞的细胞周期阻滞并增强其凋亡。

MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-γ.

作者信息

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

机构信息

Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(16):6949-54. doi: 10.7314/apjcp.2014.15.16.6949.

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-γ (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.

摘要

背景

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。

材料与方法

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。

结果

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。

结论

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。

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