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

ABSTRACT: Junctional adhesion molecule 3 (JAM3) is frequently epigenetically silenced in cancers, but its functional role and regulatory mechanisms in serous ovarian carcinoma (SOC) remained poorly defined. This study integrated RNA sequencing (RNA-seq) with functional assays to delineate JAM3-driven pathways in SOC. RNA-seq analysis of JAM3-overexpressing SOC cells revealed significant downregulation of PI3K/AKT signaling components, a finding validated by Western blot. JAM3 promoter methylation, assessed via bisulfite sequencing and qMSP, was elevated in SOC tissues and inversely correlated with JAM3 expression. Functional studies demonstrated that JAM3 overexpression suppressed proliferation, migration, and invasion while inducing apoptosis, whereas JAM3 knockdown exacerbated aggressive phenotypes. Rescue experiments using the AKT inhibitor MK2206 confirmed PI3K/AKT pathway dependency in JAM3-mediated tumor suppression. Clinically, reduced JAM3 expression correlated with advanced tumor stage and poor prognosis. These results establish JAM3 as a tumor suppressor in SOC, acting through epigenetic modulation of PI3K/AKT signaling, and highlight its potential as a therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297734 | GEO | 2025/07/08

REPOSITORIES: GEO

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