USP21 Stabilizes DEC1 To Regulate Breast Cancer Cell Proliferation

Breast cancer is the most common type of cancer in women and the second leading cause of cancer-related deaths in women.Therefore the treatment and prognosis of breast cancer is a vital.Ubiquitin modification is an important type of post-translational modification of proteins and is a reversible process.The dynamic balance of protein ubiquitination and deubiquitination in cells is involved in the regulation of cell life activities,including cell differentiation,proliferation and metabolism.USP21 is a member of the ubiquitin-specific protease(USP)family and is involved in a variety of signaling pathways.Transcription factors are abnormally regulated and occur frequently in various cancers.DEC1,which is widely expressed in most tissues,plays an important role in cell survival,differentiation,circadian rhythms and hypoxia responses.In addition,DEC1 can regulate the proliferation,metastasis and invasion of tumor cells,and it has been found in recent years that DEC1 is related to the proliferation of breast cancer.For example,DEC1 can stabilize cyclin E and inhibit the proliferation of breast cancer cells.DEC1 co-locates and interacts with ERα to inhibit the proliferation of breast cancer cells.However,there are few studies on post-translational modification of DEC1.Therefore,this paper mainly studied how USP21 affects the proliferation of breast cancer cells and the influence on the stability and function of DEC1.The main research work and new findings of this paper are as follows:1.It was found that USP21 overexpression inhibited the proliferation of MCF-7 and T47 D cells by clonal formation assay and MTT assay.2.In HEK-293 T,MCF-7 and T47 D cells,Western blotting showed that overexpression of USP21 stabilized the DEC1.Half-life experiments found that USP21 could prolong the half-life of DEC1.In vitro ubiquitination experiments also showed that USP21 affected the ubiquitin-protease system of DEC1,inhibited the degradation of DEC1,and improved the stability of DEC1.3.The interaction between USP21 and DEC1 was found by immunoprecipitation.Immune co-localization experiments showed that both of them were co-localized in the cytoplasm,which provided spatial support for their interaction.Through the clone formation experiment,it was found that USP21 inhibited the proliferation of breast cancer cells mainly by stabilizing DEC1.In this study,the inhibition of USP21 on breast cancer proliferation was linked with DEC1,and the mechanism of USP21 inhibition on breast cancer proliferation was determined.This study provides a theoretical basis for exploring the mechanism of tumor genesis and development and the treatment of breast cancer.