miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

• Published in: Biochemical and biophysical research communications 2016-08, Vol.476 (4), p.607-613
• Main Authors: Zhang, Yunda, Xu, Guoxing, Liu, Gang, Ye, Yongzhi, Zhang, Chuankai, Fan, Chuannan, Wang, Haibin, Cai, Huali, Xiao, Rui, Huang, Zhengjie, Luo, Qi
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - genetics; CELL PROLIFERATION; Cell Proliferation - genetics; Disease Progression; Down-Regulation; Female; Gene Expression; Gene Silencing; GRB2; GRB2 Adaptor Protein - genetics; GRB2 Adaptor Protein - metabolism; human diseases; Humans; IN VITRO; MAMMARY GLANDS; MCF-7 Cells; METASTASES; Metastasis; MicroRNAs - genetics; miR-411-5p; Neoplasm Invasiveness - genetics; Neoplasm Metastasis - genetics; NEOPLASMS; Proliferation; ras Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Signal Transduction - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.06.006

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 is downregulated in breast cancer tissues and cell lines.•miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro.•GRB2 is a direct target of miR-411-5p in breast cancer.•GRB2 is overexpressed in breast cancer and associates with disease outcome.•miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.