Identification of PSMD2 as a promising biomarker for pancreatic cancer patients based on comprehensive bioinformatics and in vitro studies

作者：Xiuxue Feng, Qiang Liu, Huikai Li, H. J. Yang, Enqiang Linghu · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e40117 · 被引用次数：4 · 研究领域：Ubiquitin and proteasome pathways、ATP Synthase and ATPases Research、Ferroptosis and cancer prognosis

Background: Pancreatic cancer patients have limited treatment options and extremely poor prognosis. Dysregulations of proteasome 26S subunit, non-ATPases (PSMDs) contribute to the development of various cancers, whereas the significance of PSMDs in pancreatic cancer is poorly understood. In the present study, we intended to explore the therapeutic potential of PSMDs in pancreatic cancer. Methods: Based on TCGA database, the expression of PSMDs was analyzed in pancreatic cancer patients. Multivariate Cox regression and Kaplan-Meier survival analyses were conducted to investigate the prognostic value of PSMDs. The correlations between the expression of PSMD2/14 and immune cell infiltration, immune checkpoint genes' expression, enrichment of signaling pathways, and the sensitivity of chemotherapies were also evaluated. Knockdown and overexpression experiments were performed to explore the biological function of PSMD2/14. Immunoblotting was conducted to detect the downstream signaling pathway of PSMD2. Results: knockdown of PSMD2, but not PSMD14, increased the apoptosis, gemcitabine's toxicity and inhibited the growth capacity of MIA cells. Conversely, decreased apoptosis and gemcitabine sensitivity along with accelerated cell proliferation ability were observed in PSMD2-overexpressing PANC-1 cells. Mechanistically, PSMD2 activated the AKT/mTOR signaling pathway, consistent with the findings from KEGG and GSEA analysis. The AKT specific inhibitor MK-2206 exhibited higher cytotoxi...