Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer

详细信息	查看全文 | 推荐本文 |

• 作者：Dawn R. Cochrane^a ; ¹ ; Britta M. Jacobsen^b ; ¹ ; Keith D. Connaghan^c ; Erin N. Howe^a ; David L. Bain^c ; Jennifer K. Richer^a ; ^{Jennifer.Richer@ucdenver.edu}
• 关键词：miRNA ; Progestin ; Breast cancer ; ATP1B1 ; Progesterone receptor
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 期刊代码：109_03037207
• 类别：bio
• 出版时间：15 May, 2012
• 卷：355
• 期：1
• 页码：15-24
• 文件大小：1229 K

摘要

Progesterone receptors (PRs) mediate response to progestins in the normal breast and breast cancer. To determine if liganded PR regulate microRNAs (miRNAs) as a component of their action, we profiled mature miRNA levels following progestin treatment. Indeed, 28 miRNAs are significantly altered by 6 h of progestin treatment. Many progestin-responsive genes are putative targets of progestin-regulated miRNAs; for example, progestin treatment decreases miR-29, thereby relieving repression of one of its direct targets, the gene encoding ATPase, Na⁺/K⁺ transporting, beta 1 polypeptide (ATP1B1). Thus, liganded PR regulates ATP1B1 through sites in the promoter and the 3鈥睻TR, to achieve maximal tight hormonal regulation of ATP1B1 protein via both transcriptional and translational control. We find that ATP1B1 serves to limit migration and invasion in breast cancer cells. Lastly, we demonstrate that PR itself is regulated by a progestin-upregulated miRNA, miR-513a-5p, providing a novel mechanism for tight control of PR protein expression.