BMC Cancer | |
3,6-Dihydroxyflavone regulates microRNA-34a through DNA methylation | |
Research Article | |
Xiaoli Peng1  Hui Chang2  Mantian Mi2  Qianyong Zhang2  Junli Chen2  Xiaoping Yu3  | |
[1] Department of Public Health, School of Preclinical Medicine, Chengdu Medical College, Chengdu, China;Research Center for Nutrition Correspondence and Food Safety, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, 30 Gaotanyan Street, Shapingba District, 400038, Chongqing, China;Research Center for Nutrition Correspondence and Food Safety, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, 30 Gaotanyan Street, Shapingba District, 400038, Chongqing, China;Department of Public Health, School of Preclinical Medicine, Chengdu Medical College, Chengdu, China; | |
关键词: Breast cancer; Carcinogenesis; 3,6-Dihydroxyflavone; TET1; DNMT1; miR-34a; Methylation; | |
DOI : 10.1186/s12885-017-3638-1 | |
received in 2016-01-21, accepted in 2017-08-29, 发布年份 2017 | |
来源: Springer | |
【 摘 要 】
BackgroundBreast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear.MethodsWe used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence. TET1 and 5hmC (5-hydroxymethylcytosine) levels were evaluated by immunofluorescence in nude mouse xenografts of MDA-MB-231 cells. Chromatin immunoprecipitation(ChIP) assayed for TET1 on the TET1 promoter, and dot blot analysis of DNA 5hmC was performed in MDA-MB-231 cells. We evaluated the mechanism of 3,6-DHF on the expression of tumor suppressor miR-34a by transfecting them with DNA methyltransferase (DNMT)1 plasmid and TET1 siRNA in breast cancer cells. Methylation-specific PCR detected methylation of the miR-34a promoter.ResultsFirst, we found that 3,6-DHF promotes the expression of TET1 during carcinogen-induced breast carcinogenesis in MCF10A cells and in rats. 3,6-DHF also increased TET1 and 5hmC levels in MDA-MB-231 cells. Further study indicated that TET1 siRNA and pcDNA3/Myc-DNMT1 inhibited the 3,6-DHF reactivation effect on expression of miR-34a in breast cancer cells. Methylation-specific PCR assays indicated that TET1 siRNA and pcDNA3/Myc-DNMT1 inhibit the effect of 3,6-DHF on the demethylation of the miR-34a promoter.ConclusionsOur study showed that 3,6-DHF effectively increases TET1 expression by inhibiting DNMT1 and DNA hypermethylation, and consequently up-regulates miR-34a in breast carcinogenesis.
【 授权许可】
CC BY
© The Author(s). 2017
【 预 览 】
Files | Size | Format | View |
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RO202311090104325ZK.pdf | 1166KB | download |
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