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Published on: February 21, 2014
Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA-34a axis
Bin Han1, Xiaoli Peng1, Daomei Cheng1
1School of Public Health, Chengdu Medical College, Chengdu, China.
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.
Insights
Delphinidin, a plant compound, effectively suppresses breast cancer in rats by regulating the HOTAIR/microRNA-34a pathway. This natural compound shows promise for preventing breast carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Anthocyanidins, like delphinidin, exhibit significant anti-cancer properties.
- Breast cancer remains a leading cause of mortality, necessitating novel therapeutic strategies.
- Understanding molecular mechanisms underlying cancer development is crucial for prevention and treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis in rats.
- To elucidate the molecular mechanism involving the HOTAIR/microRNA-34a axis in delphinidin's action.
- To evaluate delphinidin's impact on key signaling pathways implicated in breast cancer progression.
Main Methods:
- MNU-induced rat breast cancer model.
- Delphinidin administration and assessment of tumor suppression.
- Analysis of HOTAIR and microRNA-34a expression levels.
- Western blot analysis for Wnt/β-catenin pathway proteins (β-catenin, Gsk3β, c-Myc, cyclin-D1) and MMP-7.
- RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.
Main Results:
- Delphinidin significantly suppressed MNU-induced breast carcinogenesis in rats.
- Delphinidin downregulated HOTAIR and upregulated microRNA-34a expression.
- Delphinidin reduced the expression of β-catenin, Gsk3β, c-Myc, cyclin-D1, and MMP-7.
- MicroRNA-34a inhibition diminished delphinidin's effects on c-Myc, cyclin-D1, and MMP-7.
- HOTAIR overexpression counteracted delphinidin's effects on microRNA-34a and the Wnt/β-catenin pathway.
- Delphinidin enhanced EZH2 and H3K27me3, indicating epigenetic regulation of HOTAIR/microRNA-34a.
Conclusions:
- Delphinidin demonstrates potent anti-cancer activity against breast carcinogenesis.
- The anti-cancer mechanism involves negative regulation of the HOTAIR/microRNA-34a axis.
- Delphinidin's action is linked to the modulation of the Wnt/β-catenin signaling pathway.
- These findings support delphinidin's potential as a preventive agent for breast cancer.
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