1,25-Dihydroxyvitamin D Affects Gastric Cancer Progression by Repressing BMP3 Promoter Methylation

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Apr 18

PMID 30992671

Citations 4

Authors

Ye Zhao

Liang-Liang Cai

Hui-Ling Wang

Xiao-Juan Shi

Hui-Ming Ye

Ping Song

Bao-Qi Huang

Chi-Meng Tzeng

Affiliations

Soon will be listed here.

Abstract

Background: Vitamin D 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 on gastric cancer and mechanisms.

Methods: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D 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 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 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D 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 affects gastric cancer progression by repressing BMP3 promoter methylation.

Citing Articles

Integrative analysis of DNA methylation and gene expression through machine learning identifies stomach cancer diagnostic and prognostic biomarkers.

Hosseini M, Lotfi-Shahreza M, Nikpour P J Cell Mol Med. 2023; 27(5):714-726.

PMID: 36779430 PMC: 9983314. DOI: 10.1111/jcmm.17693.

Comprehensive Analysis of GDF10 Methylation Site-Associated Genes as Prognostic Markers for Endometrial Cancer.

Fan J, Zhou H J Oncol. 2022; 2022:7117083.

PMID: 36262352 PMC: 9576415. DOI: 10.1155/2022/7117083.

Vitamin D and Gastric Cancer: A Ray of Sunshine?.

Shah S, Iqbal Z, Alharbi M, Kalra H, Suri M, Soni N Cureus. 2021; 13(9):e18275.

PMID: 34722053 PMC: 8545571. DOI: 10.7759/cureus.18275.

Identification of hsa-miR-1275 as a Novel Biomarker Targeting for Human Epilepsy of Unknown Etiology.

Zhao Y, Lu C, Wang H, Lin Q, Cai L, Meng F Mol Ther Methods Clin Dev. 2020; 19:398-410.

PMID: 33251277 PMC: 7677659. DOI: 10.1016/j.omtm.2020.10.005.

References

Dai Z, Popkie A, Zhu W, Timmers C, Raval A, Tannehill-Gregg S . Bone morphogenetic protein 3B silencing in non-small-cell lung cancer. Oncogene. 2004; 23(20):3521-9. DOI: 10.1038/sj.onc.1207441. View

Kim S, Shevde N, Pike J . 1,25-Dihydroxyvitamin D3 stimulates cyclic vitamin D receptor/retinoid X receptor DNA-binding, co-activator recruitment, and histone acetylation in intact osteoblasts. J Bone Miner Res. 2005; 20(2):305-17. DOI: 10.1359/JBMR.041112. View

Kraunz K, Nelson H, Liu M, Wiencke J, Kelsey K . Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer. Br J Cancer. 2005; 93(8):949-52. PMC: 2361658. DOI: 10.1038/sj.bjc.6602790. View

Ben-Shoshan M, Amir S, Dang D, Dang L, Weisman Y, Mabjeesh N . 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther. 2007; 6(4):1433-9. DOI: 10.1158/1535-7163.MCT-06-0677. View

Loh K, Chia J, Greco S, Cozzi S, Buttenshaw R, Bond C . Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development. Genes Chromosomes Cancer. 2008; 47(6):449-60. DOI: 10.1002/gcc.20552. View

Chen X, Wang J, Li X, Zhang H, Ye Z . Role of BMP3 in progression of gastric carcinoma in Chinese people. World J Gastroenterol. 2010; 16(11):1409-13. PMC: 2842534. DOI: 10.3748/wjg.v16.i11.1409. View

Ronneberg J, Fleischer T, Solvang H, Nordgard S, Edvardsen H, Potapenko I . Methylation profiling with a panel of cancer related genes: association with estrogen receptor, TP53 mutation status and expression subtypes in sporadic breast cancer. Mol Oncol. 2011; 5(1):61-76. PMC: 5528272. DOI: 10.1016/j.molonc.2010.11.004. View

Diez-Perez R, Campo-Trapero J, Cano-Sanchez J, Lopez-Duran M, Gonzalez-Moles M, Bascones-Ilundain J . Methylation in oral cancer and pre-cancerous lesions (Review). Oncol Rep. 2011; 25(5):1203-9. DOI: 10.3892/or.2011.1205. View

Kisiel J, Yab T, Taylor W, Chari S, Petersen G, Mahoney D . Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. Cancer. 2011; 118(10):2623-31. PMC: 3292683. DOI: 10.1002/cncr.26558. View

10.

Ren C, Qiu M, Wang D, Luo H, Zhang D, Wang Z . Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. J Transl Med. 2012; 10:16. PMC: 3295723. DOI: 10.1186/1479-5876-10-16. View

11.

Pike J, Meyer M . The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3. Rheum Dis Clin North Am. 2012; 38(1):13-27. PMC: 4448919. DOI: 10.1016/j.rdc.2012.03.004. View

12.

Salehi-Tabar R, Nguyen-Yamamoto L, Tavera-Mendoza L, Quail T, Dimitrov V, An B . Vitamin D receptor as a master regulator of the c-MYC/MXD1 network. Proc Natl Acad Sci U S A. 2012; 109(46):18827-32. PMC: 3503153. DOI: 10.1073/pnas.1210037109. View

13.

Cai L, Ye H, Lv X, Wu Y, Zhang H, Zheng L . 25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma. Curr Drug Targets. 2013; 14(11):1367-76. DOI: 10.2174/13894501113149990204. View

14.

Feldman D, Krishnan A, Swami S, Giovannucci E, Feldman B . The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014; 14(5):342-57. DOI: 10.1038/nrc3691. View

15.

Liu Z, Zhang J, Gao Y, Pei L, Zhou J, Gu L . Large-scale characterization of DNA methylation changes in human gastric carcinomas with and without metastasis. Clin Cancer Res. 2014; 20(17):4598-612. PMC: 4309661. DOI: 10.1158/1078-0432.CCR-13-3380. View

16.

Kisiel J, Li J, Zou H, Oseini A, Strauss B, Gulaid K . Methylated Bone Morphogenetic Protein 3 (BMP3) Gene: Evaluation of Tumor Suppressor Function and Biomarker Potential in Biliary Cancer. J Mol Biomark Diagn. 2014; 4(145):1000145. PMC: 4112127. DOI: 10.4172/2155-9929.1000145. View

17.

Hargrove L, Francis T, Francis H . Vitamin D and GI cancers: shedding some light on dark diseases. Ann Transl Med. 2014; 2(1):9. PMC: 4200652. DOI: 10.3978/j.issn.2305-5839.2013.03.04. View

18.

Segovia-Mendoza M, Diaz L, Gonzalez-Gonzalez M, Martinez-Reza I, Garcia-Quiroz J, Prado-Garcia H . Calcitriol and its analogues enhance the antiproliferative activity of gefitinib in breast cancer cells. J Steroid Biochem Mol Biol. 2014; 148:122-31. DOI: 10.1016/j.jsbmb.2014.12.006. View

19.

Khayatzadeh S, Feizi A, Saneei P, Esmaillzadeh A . Vitamin D intake, serum Vitamin D levels, and risk of gastric cancer: A systematic review and meta-analysis. J Res Med Sci. 2015; 20(8):790-6. PMC: 4652314. DOI: 10.4103/1735-1995.168404. View

20.

Wen Y, Da M, Zhang Y, Peng L, Yao J, Duan Y . Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue. Int J Clin Exp Pathol. 2016; 8(10):13176-84. PMC: 4680461. View