1,25-Dihydroxyvitamin D(3) affects gastric cancer progression by repressing BMP3 promoter methylation

BACKGROUND: Vitamin D(3) has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D(3) on gastric cancer and mechanisms. METHODS: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D(3) in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D(3) on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). RESULTS: Here we show that low concentration of 1, 25-dihydroxyvitamin D(3) links to can-cerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D(3) and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D(3) stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. CONCLUSION: In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D(3) affects gastric cancer progression by repressing BMP3 promoter methylation.