Zhang Yunda, Xu Guoxing, Liu Gang, Ye Yongzhi, Zhang Chuankai, Fan Chuannan, Wang Haibin, Cai Huali, Xiao Rui, Huang Zhengjie, Luo Qi
Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China; Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, China.
Biochem Biophys Res Commun. 2016 Aug 5;476(4):607-613. doi: 10.1016/j.bbrc.2016.06.006. Epub 2016 Jun 3.
miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.
miR-411-5p(以前称为miR-411)与人类疾病密切相关,然而,miR-411-5p与乳腺癌之间的关系尚未得到充分研究。在此,我们发现与配对的相邻非肿瘤组织相比,miR-411-5p在乳腺癌组织中的表达下调。此外,与MCF-10A相比,miR-411-5p在乳腺癌细胞系中的表达也较低。此外,我们使用模拟物和抑制剂研究了miR-411-5p在乳腺癌中的靶点和机制,并证明了GRB2和Ras激活的参与。miR-411-5p的异位表达抑制了乳腺癌细胞的增殖、迁移和侵袭,而miR-411-5p的低表达则表现出相反的效果。此外,与正常组织相比,GRB2在乳腺癌组织中显著过表达,与GRB2高表达的乳腺癌患者相比,GRB2低表达的患者总生存期更长。总的来说,我们的研究揭示了miR-411-5p在乳腺癌进展中的相关机制,并且miR-411-5p/GRB2/Ras轴有可能成为乳腺癌治疗的分子靶点。