| Globally ovarian cancer is an important disease affecting women’s health.Its early symptoms are not obvious,screening means are limited,diagnosis is difficult,treatment is late and prognosis is poor.Ovarian clear cell carcinoma,a type of epithelial ovarian cancer,is a malignant tumor with a large proportion of early stages and a high 5-year survival rate,but once it progresses to advanced stages,the survival rate is lower compared to other types of ovarian cancer.The clinical treatment options are basically referenced to ovarian plasmacytoma.Understanding ovarian carcinogenesis allows better prediction and screening of risk populations,while identifying potential etiologies can help reduce the incidence of ovarian cancer.UBR5(Ubiquitin protein ligase E3 component n-recognin 5,UBR5)is an E3 ubiquitin ligase that was originally identified as a tumor suppressor in breast cancer cells UBR5 is an E3 ubiquitin ligase that was originally discovered as a tumor suppressor in breast cancer cells and is involved in a variety of important biological processes,including DNA damage,cell proliferation,cell metabolism,cell migration,invasion and apoptosis.Some studies have shown that UBR5 is highly expressed in ovarian cancer,and some researchers have suggested it as an indicator of poor prognosis in ovarian cancer patients,but the function and mechanism of action of UBR5 in ovarian cancer is not clear.Therefore,this study was conducted to investigate the function and possible mechanism of action of UBR5 in ovarian cancer cell line ES-2by cell biology and bioinformatics.Data analysis of UBR5 expression in different cancers obtained from the Ualcan database showed that UBR5 is highly expressed in cancer tissues from patients with lung adenocarcinoma,bile duct cancer,esophageal cancer,gastric cancer,colonic adenocarcinoma,and rectal cancer.RNA-seq data obtained from the Expression Atlas database and the Cancer Cell Line Encyclopedia(CCLE)of seven human ovarian cancer cell lines were screened and analyzed,and UBR5 was found to be highly expressed in the ovarian cancer cell line ES-2.We verified by Western blot and RT-q PCR that UBR5 was significantly up regultated in ES-2 cells compared to normal epithelial cells IOSE80.Therefore,ES-2 cell line was selected as the experimental material and,both CRISPR-Cas9 and sh RNA technologies were used to knockdown or knockout UBR5 to investigate the function and mechanism of UBR5 in ES-2 cells.The results showed that cell proliferation,clonogenesis,migration and invasion abilities of ES-2 cells were significantly reduced,the cell cycle was blocked in S and G2/M phases,and the apoptosis was increased after knockdown or knockout of the UBR5.Transcriptome analysis showed that knockdown of UBR5 resulted in significant changes in the expression levels of 7697 genes,These differentially expressed genes are mainly enriched in biological processes such as cell growth and cell adhesion,cellular components such as extracellular matrix and cytoskeleton,and biological functions such as cell surface receptor signaling pathways and signal transduction regulation.These results indicate that UBR5 is associated with proliferation,migration,invasion,cell cycle regulation,and apoptosis in ES-2 cells,and suggest that UBR5 is required for ovarian cancer progression,implying that UBR5 may work as a potential therapeutic target for ovarian cancer and provide reference for ovarian cancer treatment.In conclusion,by studying the function of UBR5 in ovarian cancer ES-2 cells,we found that UBR5 can regulate the malignant phenotype of ES-2 cells and may become a potential therapeutic target for ovarian cancer tre ATMent. |
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