1. Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA-34a axis.
- Author
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Han B, Peng X, Cheng D, Zhu Y, Du J, Li J, and Yu X
- Subjects
- Animals, Anthocyanins pharmacology, Breast Neoplasms chemically induced, Breast Neoplasms genetics, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Enhancer of Zeste Homolog 2 Protein metabolism, Female, Gene Expression Regulation, Neoplastic drug effects, Histones metabolism, Humans, Rats, Wnt Signaling Pathway drug effects, Xenograft Model Antitumor Assays, Anthocyanins administration & dosage, Breast Neoplasms drug therapy, Methylnitrosourea toxicity, MicroRNAs genetics, RNA, Long Noncoding genetics
- Abstract
Delphinidin, one of the main anthocyanidins, has potent anti-cancer properties. In this study, we investigated the effect of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis on rats and the mechanism of delphinidin via negative regulation of the HOTAIR/microRNA-34a axis. We found administration of delphinidin could effectively suppress MNU-induced mammal breast carcinogenesis. Delphinidin downregulated the level of HOTAIR and upregulated miR-34a in breast carcinogenesis. Western blot analysis confirmed that delphinidin treatment can significantly decrease the expression of β-catenin, glycogen synthase kinase-3β (Gsk3β), c-Myc, cyclin-D1, and matrix metalloproteinase-7(MMP-7) expression in breast cancer cells, and inhibition of miR-34a significantly reduced the effect of delphinidin on c-Myc, cyclin-D1, and MMP-7. HOTAIR overexpression also blocked the effect of delphinidin on miR-34a and the Wnt/β-catenin signaling pathway in MDA-MB-231 cells. RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay results showed that delphinidin upregulated miR-34a by inhibiting HOTAIR, coupled with enhancement of the zeste homolog 2 (EZH2) and histone H3 Lys27 trimethylation (H3K27me3). This study indicated that delphinidin may potentially suppress breast carcinogenesis and exert its anti-cancer effect through the HOTAIR/miR-34a axis. These findings provided new evidence for the use of delphinidin in preventing breast carcinogenesis., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2019
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