微小RNA-124的下调通过长链非编码RNA-MALAT1调控和细胞周期蛋白依赖性激酶4/ E2F1信号激活导致乳腺癌进展。

miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation.

作者信息

Feng Tongbao, Shao Fang, Wu Qiyong, Zhang Xiaohang, Xu Dongqin, Qian Keqing, Xie Yewen, Wang Shizhong, Xu Ning, Wang Yong, Qi Chunjian

机构信息

Medical Research Center, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, China.

Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, China.

出版信息

Oncotarget. 2016 Mar 29;7(13):16205-16. doi: 10.18632/oncotarget.7578.

The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recently shown to be dysregulated in several cancers. However, the mechanisms underlying the role of MALAT1 in breast cancer remain unclear. Herein, we showed that MALAT1 was aberrantly increased in breast cancer tissues and cells. MALAT1-siRNA inhibited breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression. Taken together, our data highlight the pivotal role of MALAT1 in breast cancer tumorigenesis. Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.

长链非编码RNA（lncRNA）转移相关肺腺癌转录本1（MALAT1）最近已被证明在多种癌症中表达失调。然而，MALAT1在乳腺癌中发挥作用的潜在机制仍不清楚。在此，我们发现MALAT1在乳腺癌组织和细胞中异常上调。MALAT1-siRNA在体外和体内均抑制乳腺癌细胞增殖和细胞周期进程。此外，MALAT1通过直接结合miR-124并下调miR-124表达，作为一种内源性强效调节因子发挥作用。此外，MALAT1逆转了miR-124对乳腺癌增殖的抑制作用，并参与细胞周期蛋白依赖性激酶4（CDK4）的表达。综上所述，我们的数据突出了MALAT1在乳腺癌发生中的关键作用。此外，本研究阐明了乳腺癌中MALAT1-miR-124-CDK4/E2F1信号通路，这可能为攻克乳腺癌提供一种新方法。