LAUSR

Background: Altered DNA methylation in microRNA (miRNA) host genes has been frequently associated with abnormal miRNA expression during the pathogenesis of cancer. miR-145 was identified as a tumor-suppressive miRNA that was down-regulated in several cancer types. Accumulating evidence has clearly demonstrated that a low expression of miR-145 in breast cancer was correlated with an aberrant hypermethylation in its host gene. Diosgenin is a steriod saponin, which is extracted from the tubers of Dioscorea wild yam. The anti-tumor mechanisms of diosgenin have been demonstrated via the modulation of multiple cell signaling pathways, which are associated with growth, differentiation, apoptosis and oncogenesis. However, there is little information regarding the epigenetic-based effects of Diosgenin in breast cancer. In our study, we hypothesize that Diosgenin has anti-proliferative effects on breast cancer cells through the demethylation of miR-145. Material and Methods: MCF-10A breast epithelial cells and MCF-7 breast cancer cells were used to investigate the effects of Diosgenin on the expression and methylation of miR-145 using real time-PCR (RT-PCR) and methylation-specific PCR (MSP), respectively. An MTS proliferation assay was performed to assess the effect of Diosgenin on the proliferation of MCF-7 breast cancer cell. Result: In comparison with MCF-10A breast epithelial cells, MCF-7 breast cancer cells showed the hypermethylation of miR-145, and significantly down-regulated miR-145 expression. Diosgenin treatment led to proliferation inhibition of MCF-7 breast cancer cells. In MCF-7 breast cancer cells, the Diosgenin treatment led to significantly up-regulated miR-145, whereas the methylation level of miR-145 significantly decreased. Conclusion: Diosgenin, a natural compound, exhibits an anti-proliferative effect on breast cancer cells, and affects the methylation and expression of miR-145. These findings indicate that the demethylation of miR-145 may be a molecular mechanism underlying the anti-tumor of Diosgenin in breast cancer. Citation Format: Fengqin Shi, Lingeng Lu, Ya Li, Li Hou, Xinyi Chen, Han Rui, Chong Wang, Ya Yue. Diosgenin inhibits the proliferation of MCF-7 breast cancer cells through the demethylation of miR-145 gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2871.