Mechanistic Study on the Role of OVCA2 in the Development and Progression of Pancreatic Cancer

This study investigates the role and regulatory mechanisms of OVCA2 in pancreatic cancer, a dis ease with rapid progression and poor prognosis. OVCA2 expression and its prognostic significance were analyzed via immunohistochemistry. The effects of OVCA2 on cell proliferation, apoptosis, and mitochondrial function were examined through colony formation, flow cytometry, and mitochondrial function assays. OVCA2 localization was determined via immunofluorescence. IP sequencing and transcriptomic analyses explored molecular changes and validated by Western blot. OVCA2 expression is low in multiple cancers but specifically correlates with pancreatic cancer prognosis. OVCA2 overexpression reduced proliferation and colony formation, while increasing apoptosis. OVCA2 localized to the outer mitochondrial membrane and inhibited mitochondrial function, reducing oxygen res piration, ATP production, and mtDNA levels, while increasing ROS and oxidative stress markers. OVCA2 knock down had the opposite effect. IP-seq revealed OVCA2 overexpression upregulated the TNF signaling pathway and downregulated Wnt/β-catenin signaling, findings confirmed by transcriptomics and Western blot. High expression of OVCA2 in pancreatic cancer cells inhibits cancer cell survival by promoting excessive accumulation of ROS (re active oxygen species) in vivo. This process further enhances cell apoptosis through the activation of TNF signaling pathways, ultimately leading to cancer cell death. Conversely, low expression of OVCA2 suppresses TNF signaling pathway-induced apoptosis, maintains intracellular OXPHOS (oxidative phosphorylation) function, and promotes tumorigenesis. The elucidation of OVCA2’s regulatory mechanism in pancreatic cancer suggests that enhancing OVCA2 expression could represent a novel therapeutic strategy for the treatment of this malignancy.

CSTR: 32200.14.cjcb.2025.06.0006