Abstract Objective Lung cancer exhibits a high global incidence and mortality rate, with a poor prognosis, highlighting the urgent need for new therapeutic targets. Gap junction proteins are vital for intercellular communication and signal transduction; however, the clinical significance and biological function of gap junction protein β3 (GJB3) in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to elucidate the molecular regulatory mechanisms of GJB3 in LUAD. Methods We utilized quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunohistochemistry (IHC) to assess GJB3 expression in lung adenocarcinoma. We analyzed the correlation between GJB3 expression, clinical pathological parameters, and patient prognosis. The biological function of GJB3 was validated through in vitro and in vivo experiments. Additionally, we employed co-immunoprecipitation (CO-IP), CCK-8 assays, flow cytometry, Transwell assays, qRT-PCR, WB, and ubiquitination assays to investigate the underlying molecular mechanisms. Results GJB3 was significantly overexpressed in lung adenocarcinoma cell lines and tumor tissues, with high expression correlating with adverse prognosis. GJB3 enhanced cell proliferation, migration, and invasion while inhibiting apoptosis, exhibiting oncogenic properties in a mouse model of LUAD xenografts. Mechanistic studies indicated that GJB3 facilitates the interaction between MDM2 and p53, promoting the ubiquitin-proteasomal degradation of p53 and thereby regulating the p53 signaling pathway, which contributes to the development and progression of lung adenocarcinoma. Conclusion GJB3 is overexpressed in LUAD, and through its role in promoting the interaction between MDM2 and p53, it mediates the ubiquitin-mediated degradation of p53, modulating the p53 signaling pathway and facilitating lung adenocarcinoma progression. These findings suggest that GJB3 may serve as a novel therapeutic target and prognostic biomarker for LUAD. This abstract is funded by: Key Research Project of Natural Science in Anhui Provincial Universities (2024AH051230)、Overseas Study and Research Funding Program for Young Key Teachers by the Anhui Provincial Department of Education (JWFX2024023)
Gong et al. (Fri,) studied this question.