Inhibition of USP21 leads to ovarian carcinoma cell death by suppressing MAPK signaling

Abstract Ovarian cancer is the most aggressive and lethal of all gynecologic malignancies. Although the overexpression (OE) of ubiquitin‐specific peptidase 21 (USP21) has been observed in multiple cancers, its expression profile and biological function in ovarian cancer remain unknown. The expression levels of USP21 in ovarian cancer cells and tissues as well as adjacent normal tissues were assessed by qRT‐PCR or Western blot assay. The biological function of USP21 in ovarian cancer cells was assessed by cell growth assay in vitro and a tumor growth model in vivo. Our study revealed that USP21 was markedly elevated in ovarian carcinoma tissues compared with adjacent normal tissues. Downregulation of USP21 attenuated the expression levels of MEK2 and p‐ERK1/2. Depletion of USP21 resulted in suppressed cell growth of ovarian cancers in vitro and inhibited tumor growth in vivo. Conversely, OE of USP21 promoted the cell proliferation of ovarian cancers and conferred resistance to BAY 11‐7082. These findings provide evidences supporting the notion of USP21 as a promising therapeutic target for the treatment of ovarian cancer.