Epigenetic silencing of JAM3 promoted progression in serous ovarian carcinoma through PI3K/AKT pathway

Junctional adhesion molecule 3 (JAM3) is frequently epigenetically silenced in various cancers, but its role in serous ovarian carcinoma (SOC) was unclear.

This study evaluated JAM3 expression and methylation in SOC using immunohistochemistry (IHC), bisulfite sequencing PCR (BSP), and quantitative methylation-specific PCR (qMSP). Cell proliferation, apoptosis, migration, and invasion were examined using CCK8, flow cytometry, scratch-wound, and transwell assays. Pathways downstream of JAM3 were explored through RNA sequencing (RNA-seq) and Western Blot analysis, with rescue experiments using AKT inhibitor (MK2206) to validate pathway dependency.

Findings revealed that JAM3 expression is significantly reduced in SOC, correlating with advanced clinical stages and poor prognosis. Methylation levels of the JAM3 promoter were higher in SOC samples compared to normal tissues and were linked to increased Ki67 expression and clinical stages. Functionally, overexpressing JAM3 in SOC cells triggered apoptosis and hindered proliferation, migration, and invasion, whereas JAM3 knockdown produced opposite effects. Mechanism analysis demonstrated that JAM3 affects SOC cell proliferation through the PI3K/AKT signaling pathway.

Conclusively, JAM3 acts as a tumor suppressor in SOC by modulating the PI3K/AKT pathway. These insights present JAM3 as a promising therapeutic target for SOC diagnosis and treatment.