Qinong Ye
Beijing Institute of Biotechnology, China
Title: A microRNA-PES1 axis regulates the balance between estrogen receptors α and β in breast cancer
Biography
Biography: Qinong Ye
Abstract
The development of breast cancer is frequently associated with enhanced expression of tumor-promoting estrogen receptor α (ERα) protein and reduced expression of tumor-suppressive ERβ protein. Here we show that a microRNA-PES1 axis can regulate the balance between ERα and ERβ in breast cancer. PES1 controlled many estrogen-responsive genes by increasing the transcriptional activity of ERα while decreasing transcriptional activity of ERβ. Consistent with this modulation of ERα and ERβ transcriptional activity, PES1 promoted the stability of the ERα protein and inhibited that of ERβ through the ubiquitin-proteasome pathway, mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP). A microRNA (miR-A) downregulated PES1 expression by targeting its 3’-untranslated region. Contrary to PES1, miR-A decreased the transcriptional activity and expression of ERα but increased those of ERβ. miR-A inhibited PES1-induced breast cancer growth. Further analysis of clinical samples showed that expression of miR-A, which is downregulated in breast cancer, inversely correlated with PES1, which is upregulated in breast cancer. Our data indicate that PES1 contributes to breast tumor growth through modulating the balance between ERα and ERβ. miR-A mimics may be a better drug than commonly used endocrine drugs that repress both ERα and ERβ activities.