PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family based on bioinformatics analysis and in vitro validation

AbstractBackground The ubiquitin-proteasome system is an indispensable mechanism for regulating intracellular protein degradation, thereby affecting human antigen processing, signal transduction, and cell cycle regulation. We used bioinformatics database to predict the expression and related roles of all members of thePSMDfamily in ovarian cancer. Our findings may provide a theoretical basis for early diagnosis, prognostic assessment, and targeted therapy of ovarian cancer. Methods GEPIA, cBioPortal, and Kaplan–Meier Plotter databases were used to analyze the mRNA expression levels, gene variation, and prognostic value ofPSMDfamily members in ovarian cancer.PSMD8was identified as the member with the best prognostic value. The TISIDB database was used to analyze the correlation betweenPSMD8and immunity, and the role of PSMD8 in ovarian cancer tissue was verified by immunohistochemical experiments. The relationship of PSMD8 expression with clinicopathological parameters and survival outcomes of ovarian cancer patients was analyzed. The effects of PSMD8 on malignant biological behaviors of invasion, migration, and proliferation of ovarian cancer cells were studied byin vitroexperiments. Results The expression levels ofPSMD8/14mRNA in ovarian cancer tissues were significantly higher than those in normal ovarian tissues, and the expression levels ofPSMD2/3/4/5/8/11/12/14mRNA were associated with prognosis. Up-regulation ofPSMD4/8/14mRNA expression was associated with poor OS, and the up-regulation ofPSMD2/3/5/8mRNA expression was associated with poor PFS in patients with ovarian serous tumors. Gene function and enrichment analysis showed thatPSMD8is mainly involved in biological processes such as energy metabolism, DNA replication, and protein synthesis. Immunohistochemical experiments showed that PSMD8 was mainly expressed in the cytoplasm and the expression level was correlated with FIGO stage. Patients with high PSMD8 expression had poor prognosis. Overexpression of PSMD8 significantly enhanced the proliferation, migration, and invasion abilities in ovarian cancer cells. Conclusion We observed different degrees of abnormal expression of members ofPSMDfamily in ovarian cancer. Among these, PSMD8 was significantly overexpressed in ovarian malignant tissue, and was associated with poor prognosis.PSMDs, especiallyPSMD8, can sereve as potential diagnostic and prognostic biomarkers and therapeutic targets in ovarian cancer.