3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21
Our previous study selected a promising chemopreventive agent 3,6-dihydroxyflavone (3,6-DHF),and found 3,6-DHF significantly up-regulates miR-34a and down-regulates miR-21 in breast carcinogenesis,yet the upstream and downstream events of the anticancer mechanism remain unclear.The present study showed that 3,6-DHF co-treatment effectively inhibits carcinogens-induced breast carcinogenic transformation in human breast epithelial MCF10A cells.The data revealed the significant down-regulation of miR-34a and up-regulation of miR-21 in breast carcinogenesis,which could be mitigated by 3,6-DHF treatment.Methylation-Specific PCR detections showed that 3,6-DHF inhibits the hypermethylation of the miR-34a promoter.Further studies indicated that 3,6-DHF is an effective methyltransferase (DNMT)1 inhibitor,docking to the putative cytosine pocket of the protein,and thus decreases the DNMT activity in a dose-dependent manner.Moreover,the ChIP-qPCR analysis for histone modifications showed that 3,6-DHF treatment significantly lowers the H3K9-14ac on the miR-21 promoter.It was concluded that 3,6-DHF up-regulates miR-34a via inhibiting DNMT1 and hypermethylation,while down-regulates miR-21 by modulating histone modification in breast carcinogenesis.
breast carcinogenesis flavonoids microRNAs epigenetic
CHANG Hui PENG Xiaoli GU Yeyun CHEN Junli ZHU Jundong ZHANG Qianyong MI Mantian
Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, 400038, China
国内会议
广州
英文
1-8
2015-05-23（万方平台首次上网日期，不代表论文的发表时间）