1,25-Dihydroxyvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation
Authors Zhao Y, Cai LL, Wang HL, Shi XJ, Ye HM, Song P, Huang BQ, Tzeng CM
Received 22 November 2018
Accepted for publication 14 February 2019
Published 28 March 2019 Volume 2019:12 Pages 2343—2353
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Leo Jen-Liang Su
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
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