Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer

Abstract

Estrogen receptors (ERs), including ERα and ERβ, mainly mediate the genotype effect of estrogen. ERα is highly expressed in most breast cancers. Endocrine therapy is the most effective and safety adjunctive therapy for ER positive breast cancers. RNPC1, an RNA binding protein (RBP), post-transcriptionally regulating gene expression, is emerging as a critical mechanism for gene regulation in mammalian cells. In this study, we revealed RNPC1’s capability of regulating ERα expression. There was a significant correlation between RNPC1 and ERα expression in breast cancer tissues. Ectopic expression of RNPC1 could increase ERα transcript and expression in breast cancer cells, and vice versa. Consistent with this, RNPC1 was able to bind to ERα transcript to increase its stability. Furthermore, overexpression of ERα could decrease the level of RNPC1 transcript and protein. It suggested a novel mechanism by which ERα expression was regulated via stabilizing mRNA. A regulatory feedback loop between RNPC1 and ERα was proved. It indicated that RNPC1 played a crucial role in ERα regulation in ER-positive breast cancers via binding to ERα mRNA. These findings might provide new insights into breast cancer endocrine therapy and ERα research.