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

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Zonglin ZhangChenxia Zhou

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.

Citations

Jan 10, 2018·Cold Spring Harbor Perspectives in Biology·Adam M Heck, Jeffrey Wilusz
Jan 8, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lei-Yun WangJi-Ye Yin
Jan 24, 2020·Wiley Interdisciplinary Reviews. RNA·Christopher W SchultzJonathan R Brody
Aug 14, 2020·Cellular and Molecular Life Sciences : CMLS·Yueshuang KeXueqing Ba
Mar 19, 2020·International Journal of Molecular Sciences·Lei DingQinghua Cui
Sep 17, 2020·International Journal of Molecular Sciences·Dobrochna DolickaMichelangelo Foti

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