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17β-Estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells

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Abstract

In estrogen responsive breast cancer cells, estradiol (E2) is a key regulator of cell proliferation and survival. MiR-155 has emerged as an “oncomiR”, which is the most significantly up-regulated miRNA in breast cancer. Moreover, miR-155 is higher in ERα (+) breast tumors than ERα (−), but no one has examined whether E2 regulates miR-155 expression in MCF-7 cells. In this study, the aim was to explore whether miR-155 involved in E2 regulated expression of estrogen responsive genes. We evaluated miR-155 expression in human breast cancer cells by real-time PCR, finding out miR-155 was overexpressed in MCF-7 cells compared with MDA-MB-231 cells. Treatment with E2 in MCF-7 cells increased miR-155 expression, promoting proliferation and decreasing apoptosis, similarly, transfection of miR-155m to MCF-7 cells gave the similar results. In contrast, inhibited miR-155 expression by transfection with miR-155 inhibitors reduced proliferation and promoted apoptosis of MCF-7 cells. Moreover, TP53INP1 is one of the targets of miR-155. E2 negatively regulated TP53INP1 mRNA expression and the protein expression of TP53INP1, cleaved-caspase-3, -8, -9, and p21, whereas transfection with miR-155 inhibitors increased TP53INP1, cleaved-caspase-3, -8, -9, and p21 protein level. These results demonstrated that E2 promoted breast cancer development and progression possibly through increasing the expression of miR-155, which was overexpressed in MCF-7 cells, contributes to proliferation of MCF-7 cells possibly through down-regulating TP53INP1.

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Acknowledgments

We are grateful to the Stem Cell and Tissue Engineering Lab at Chongqing Medical University for providing experimental equipments, and thank all staff in this lab for their help and advice. We also thank the Institute of Life Sciences for providing the technical assistance of cell cycle analysis, cell apoptosis analysis, Immunofluorescence, and Real-time quantitative PCR.

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  1. Department of Pathophysiology, School of Basic Medicine, Chongqing Medical University, Chongqing, China

    Chunmei Zhang, Jing Zhao & Huayu Deng

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  1. Chunmei Zhang
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Correspondence to Huayu Deng.

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Zhang, C., Zhao, J. & Deng, H. 17β-Estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells. Mol Cell Biochem 379, 201–211 (2013). https://doi.org/10.1007/s11010-013-1642-6

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  • DOI: https://doi.org/10.1007/s11010-013-1642-6

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