HuR promotes breast cancer cell proliferation and survival via binding to CDK3 mRNA

• Published in: Biomedicine & pharmacotherapy Vol. 91; pp. 788 - 795
• Main Authors: Zhang, Zonglin, Huang, Aimei, Zhang, Aihong, Zhou, Chenxia
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2017
• Subjects: Apoptosis - genetics; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; CDK3; Cell Cycle - genetics; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase 3 - genetics; Cyclin-Dependent Kinase 3 - metabolism; ELAV-Like Protein 1 - metabolism; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; HuR; Internal Medicine; Lentivirus - metabolism; Medical Education; mRNA stability; Protein Binding; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Breast cancer; HuR; CDK3; mRNA stability
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.04.063

Abstract HuR, a ubiquitously expressed RNA-binding protein, stabilizes mRNA and regulates its translation. HuR expression was increased at all stages of breast cancer and correlated with poor clinical outcome. However, the detailed mechanisms remain unclear. Here we reported that overexpression of HuR increased CDK3 mRNA stability and thus its protein expression in MDA-MB-231 and MCF-7 cells. Mechanistically, CDK3 mRNA was identified as a target of HuR via bioinformatics and RNA binding protein immunoprecipitation (RIP) assays. Furthermore, treatment with HuR shRNA decreased CDK3 expression, inhibited cell proliferation and promoted cell apoptosis in breast cancer. More importantly, overexpression of CDK3 reversed the suppressive effects of HuR knockdown on cell growth in both MDA-MB-231 and MCF-7 cells. Finally, HuR and CDK3 expression levels were positively correlated and significantly up-regulated in breast cancer samples. And overexpression of HuR attenuated the chemotherapeutical efficiency of breast cancer. Therefore, our results indicate that ectopic expression of HuR promotes breast cancer cell proliferation and survival by directly binding to and stabilizing CDK3 mRNA.