Knockdown of human antigen R reduces the growth and invasion of breast cancer cells in vitro and affects expression of cyclin D1 and MMP-9

Abstract

HuR, a ubiquitously expressed member of the Hu family, selectively binds and stabilizes ARE-containing mRNAs encoding proto-oncogenes, cell cycle regulators, cytokines and growth factors. The role of HuR and its cellular function in breast cancer remains unclear. This study aimed to provide new insights into the implication of HuR in breast cancer. We show that MCF7 and MDA-MB-231 breast cancer cells stably transfected with a hammerhead ribozyme transgene specifically targeted to HuR (MCF7HuRKO and MDA-MB-231HuRKO) have reduced HuR expression both at mRNA and protein levels. This study reveals that HuR knockdown dramatically reduced cell growth in MCF7 cells (P<0.001) and invasive properties in MDA-MB-231 cells (P<0.001). Furthermore, we report that the decreased cell growth rate in MCF7 cells is seen together with a reduction in cyclin D1 transcript and protein levels and that the change in invasiveness in MDA-MB-231 cells seems to be linked with decreased MMP-9 levels. Our study shows that targeting HuR can influence breast cancer cell growth and invasion and suggests a role for HuR in vitro in enhancing breast cancer cell growth and invasion. These changes may be facilitated through changes in the levels of cyclin D1 and MMP-9.