DICER regulation by an USP7-MDM2 axis in cancer cells
DICER is an RNase III enzyme which plays a critical role in the microRNA mature process in the cytoplasm, but also is involved in other functions such as chromatin remodeling, epigenetic modification and DNA damage repair in the nucleus. The expression of DICER is almost decreased across the board in human cancers, which highlights that its expression is strictly controlled, however the underlying mechanisms still remain unknown. In this study, we find that deubiquitinase USP7 suppresses the expression of DICER at the protein level, which impacts DNA damage response (DDR) and cancer progression. MDM2, which is a well-known oncoprotein and also a substrate of USP7, is identified as a novel DICER ubiquitin E3 ligase, thus forming a new regulatory axis of USP7-MDM2-DICER. These findings may provide a new approach to the diagnosis, treatment and prognosis of malignant tumors. Overall design: mRNA expression profiles and miRNA expression profiles in MDA-MB-231/DU145 stable cell lines