Effect Of Deubiquitin Enzyme JOSD1 On The Proliferation Of Breast Cancer Cells

Breast cancer is the cancer with the highest incidence among female cancers,and its mortality rate is second only to lung cancer,and studies have found that breast cancer is getting younger and more urbanized in recent years.Therefore,studying the molecular mechanism of the occurrence and development of breast cancer and identifying relevant markers will help to deepen the understanding of the physiological mechanism of breast cancer and provide a theoretical basis for clinical drug treatment of breast cancer.Deubiquitin enzyme plays an important regulatory role in the progress of breast cancer.In recent years,protein 1 containing Josephine domain(Josephin domain-containing protein 1,JOSD1),one of the ubiquitin enzyme family MJD,has also been found to be related to the occurrence and development of cancer,but the specific mechanism remains not clear.Abnormal cell proliferation is a major biological feature of malignant tumors.The activation of phosphatidylinositol-3-kinase(phosphatidylinositol-3-kinases,PI3K)signal pathway promotes cell proliferation.Phosphatidylinositol trisphosphate 3-phosphatase and dual-specificity protein phosphatase(PTEN)is a typical tumor suppressor and can be used as antagonists of PI3 K signaling pathway.This study aims to explore the effect of JOSD1 on the proliferation of breast cancer aspects of the function of cell biology.The main contents are as follows:(1)oncomine database analysis showed that the expression of JOSD1 was different in breast cancer and paracancerous tissues,and Kaplan-Meier analysis found that there was a negative correlation between the expression of JOSD1 and survival rate.In breast cancer patients,the survival rate of patients with high expression of JOSD1 was significantly lower than that of patients with low expression of JOSD1.MTT assay and clone formation assay were used to explore the effect of JOSD1 on proliferation capacity of breast cancer cells.It was found that JOSD1 could promote cell proliferation,increase the number of cell clones,and accelerate the progress of breast cancer.In addition,inhibitors screening assay showed that JOSD1 regulated cell process through PI3K/Akt signal pathway.(2)PTEN inhibition can activate PI3 K signal pathway.The correlation between JOSD1 regulating PI3K/Akt signal pathway and PTEN was further studied.Western blotting showed that JOSD1 inhibited the expression of PTEN,and half-life assay showed that JOSD1 decreased the stability of PTEN.What’s more,it is found that JOSD1 downregulates the SUMOylation of PTEN.(3)the interaction between exogenous JOSD1 and PTEN was found in co-immunoprecipitation experiment,and the interaction between them was further verified by semi-endogenous Co-IP assay.Immunofluorescence assay found that JOSD1 and PTEN was co-located in the nucleus,which providing subcellular localization support for the interaction between them.To sum up,JOSD1 can interact with PTEN,which inhibits the expression of PTEN,reduces the stability of PTEN,and reduces the SUMOylation level of PTEN,all of which can activate PI3K/Akt signal and promoting cell proliferation.