کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2550644 | 1560579 | 2016 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Over-expression of miR-451a can enhance the sensitivity of breast cancer cells to tamoxifen by regulating 14-3-3ζ, estrogen receptor α, and autophagy Over-expression of miR-451a can enhance the sensitivity of breast cancer cells to tamoxifen by regulating 14-3-3ζ, estrogen receptor α, and autophagy](/preview/png/2550644.png)
AimTo investigate the effects and mechanisms of miR-451a in the tamoxifen (TAM) resistance of breast cancer cells.Materials and methodsTAM sensitive cells (MCF-7) and resistant cells (LCC2) were employed in the study. The lentivirus vectors of Lv-miR-451a, Lv-miR-451a sponge, and Lv-miR-451a NC were employed to increase or decrease the expression of miR-451a, respectively. SiRNA to 14-3-3ζ was used to inhibit expression of 14-3-3ζ. MTT assay was utilized to detect breast cancer cell proliferation. AnnexinV-FITC binding assay was used to detect apoptosis. Expression of ERα, 14-3-3ζ and miR-451a were measured by qRT-PCR and Western blot analysis. Interactions between 14-3-3ζ and ERα were investigated by co-immunoprecipitation. LC3-II surface expression and intracellular autophagosomes were observed by Western blot and electron microscopy.Key findingsOver-expression of miR-451a can enhance MCF-7 and LCC2 cell sensitivity to TAM. Opposite effects were elicited by knocking down miR-451a. TAM treatment can up-regulate 14-3-3ζ expression, and down-regulate ERα expression. 14-3-3ζ and ERα were shown to interact. Over-expression of miR-451a decreased 14-3-3ζ expression and increased ERα expression, suppressing cell proliferation, increasing apoptosis, and reducing activation of p-AKT and p-mTOR. R18 can significantly decrease cell proliferation and increase apoptosis. R18 and 14-3-3ζ siRNA can rescue the effects of down-regulation of ERα by knocking down miR-451a. Over-expression of miR-451a inhibits autophagy, knocking-down miR-451a stimulates autophagy.SignificanceMiR-451a functions as a suppressor of resistance to TAM through regulating autophagy, the expression of 14-3-3ζ and ERα. This suggests miR-451a to be a potential target for reversing resistance to TAM.
Journal: Life Sciences - Volume 149, 15 March 2016, Pages 104–113