GPM6B inhibits tumor progression by targeting HPGD in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the most prevalent form of lung Cancer and the predominant cause of cancer-associated mortality. Given the low survival rate of patients with LUAD, there is a need to identify new therapeutic targets. Glycoprotein M6B (GPM6B) is a tumor‑associated gene in numerous types of malignancies; however, its specific role in LUAD remains largely unexplored. Integrated bioinformatics analyses of The Cancer Genome Atlas and Gene Expression Omnibus datasets, along with immunohistochemistry assays demonstrated that GPM6B was downregulated in LUAD compared with adjacent normal tissue. Elevated expression of GPM6B was associated with prolonged survival in patients with LUAD, suggesting that GPM6B serves as a prognostic biomarker in LUAD. Cell Counting Kit‑8 (CCK‑8) and Transwell assays demonstrated that exogenously expressed GPM6B significantly inhibited the proliferation and migration of the LUAD cell lines A549 and PC9. Notably, tumorigenesis assays conducted in nude mice demonstrated that the overexpression of GPM6B also suppressed tumor growth in vivo. Mechanistically, GPM6B may have inhibited the malignant behavior of LUAD cells by promoting the expression of 15‑hydroxyprostaglandin dehydrogenase and activating the p53 signaling pathway, as evidenced by transcriptome data analysis, western blotting and phenotypic assays. Furthermore, the qPCR results from LUAD cells treated with DNA methylation and histone deacetylase inhibitors indicated that low expression of GPM6B was associated with DNA methylation and histone deacetylation. Overall, the present study demonstrated that GPM6B may serve as a novel tumor suppressor and elucidated its potential mechanism in regulating the progression of LUAD.

DNA methylation; GPM6B; HPGD; histone deacetylation; lung adenocarcinoma; p53 signaling pathway.