3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21

Cancer Prevention Research
Xiaoli PengMan-Tian Mi

Abstract

Our previous study selected a promising chemopreventive agent 3,6-dihydroxyflavone (3,6-DHF) and found that 3,6-DHF significantly upregulates miR-34a and downregulates 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 cotreatment effectively inhibits carcinogens-induced breast carcinogenic transformation in human breast epithelial MCF10A cells. The data revealed the significant downregulation of miR-34a and upregulation 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. In addition, our study revealed that 3,6-DHF represses the PI3K/Akt/mTOR signaling pathway in breast carcinogenesis in vitro and in vivo. Inhibition of miR-34a or o...Continue Reading

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Citations

Aug 12, 2015·Chemical Biology & Drug Design·Ammad Ahmad FarooqiPierluigi Benedetti Panici
Sep 28, 2016·Cell Biology International·Danying Chen, Zuolin Wang
Sep 6, 2017·BMC Cancer·Xiaoli PengMantian Mi
Apr 21, 2020·Journal of Oncology·Xiaocheng CaoJianguo Cao
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Apr 6, 2021·Frontiers in Endocrinology·Ximena M Bustamante-MarinDelisha A Stewart
Apr 24, 2021·Nucleic Acid Therapeutics·Nahid Arghiani, Maryam M Matin

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