OncoTargets and Therapy (Mar 2019)
1,25-Dihydroxyvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation
Abstract
Ye Zhao,1,2,* Liang-Liang Cai,3,* Hui-Ling Wang,1 Xiao-Juan Shi,1 Hui-Ming Ye,4 Ping Song,5 Bao-Qi Huang,5 Chi-Meng Tzeng1 1School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, People’s Republic of China; 2Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture, Nanjing Tech University, Nanjing 211800, People’s Republic of China; 3Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, People’s Republic of China; 4Department of Clinical Laboratory, Zhongshan Hospital Xiamen University, Xiamen 361004, People’s Republic of China; 5College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, People’s Republic of China *These authors contributed equally to this work Background: Vitamin D3 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 D3 on gastric cancer and mechanisms. Methods: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 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 D3 links to cancerization 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 D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 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 D3 affects gastric cancer progression by repressing BMP3 promoter methylation. Keywords: BMP3, 1,25-dihydroxyvitamin D3, gastric cancer, promoter methylation
