PLD3: In vitro functional characterization and autophagy pathway-mediated regulatory effects in gastric cancer.

BACKGROUND

PLD3, a type-II transmembrane glycoprotein enriched in late endosomes and lysosomes, governs nucleic-acid turnover, immune signalling and intracellular homeostasis, and consequently influences both cell-cycle progression and programmed death. Although carcinoma of the stomach ranks among the most frequently diagnosed and lethal malignancies of the gastrointestinal tract, the precise functional dialogue between PLD3 and gastric tumorigenesis has yet to be elucidated.

METHODS

Bioinformatics workflows were applied to analyze gastric carcinoma datasets retrieved from The Cancer Genome Atlas (TCGA). Comprehensive analysis of PLD3 encompassed quantification of expression, survival outcomes, and analysis of its correlation with clinical stage and TNM staging system. RT-qPCR was employed to validate the expression levels of PLD3 in gastric carcinoma tissue and established cell lines. In vitro functional experiments were conducted to further investigate the biological functions of PLD3 in gastric cancer and its mechanistic association with autophagy.

RESULTS

Research shows PLD3 is markedly overexpressed in gastric carcinoma tissues, and its high expression is closely linked to reduced patient overall survival. Functional assays verified PLD3 knockdown notably impairs cancer cell malignant phenotypes; conversely, PLD3 overexpression boosts cancer cell malignancy and suppresses apoptosis. Treating PLD3-overexpressing gastric cancer cells with Vps34-IN-1-a potent inhibitor of autophagy key regulator Vps34-significantly inhibits PLD3-driven proliferation and promotes apoptosis.

CONCLUSIONS

PLD3 exhibits markedly elevated expression in gastric cancer tissues, thus serving as a highly promising novel biomarker for prognostic assessment of this malignancy.