Autophagy-related gene PXN as a prognostic marker: Promotion of ovarian cancer progression by suppressing the p110β/Vps34/Beclin1 pathway

Among gynecological malignancies, ovarian Cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian Cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy-related genes that determine patient prognosis using limma differential expression and Kaplan-Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK-8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian Cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of Autophagy proteins and the PI3K/Akt/mTOR and p110β/Vps34/Beclin1 pathway proteins in ovarian Cancer cells was detected using western blot; Autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy-related genes were found to be overexpressed in ovarian -cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p < .05). PXN activates and regulates signaling pathways related to cellular Autophagy, ubiquitination, lysosomes, PI3K-Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian Cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3Ⅰ, inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110β) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian Cancer and is associated with poor patient prognosis. It may promote ovarian Cancer cell proliferation, migration, and invasion by inhibiting cellular Autophagy via suppression of the p110β/Vps34/Beclin1 pathway.

PXN; autophagy; bioinformatics analysis; ovarian cancer; p110β/Vps34/Beclin1 pathway.