Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer

被引：77

作者：

Cochrane, Dawn R. ^{[1
]}

Jacobsen, Britta M. ^{[2
]}

Connaghan, Keith D. ^{[3
]}

Howe, Erin N. ^{[1
]}

Bain, David L. ^{[3
]}

Richer, Jennifer K. ^{[1
]}

机构：

[1] Univ Colorado, Dept Pathol, Denver, CO 80202 USA

[2] Univ Colorado, Dept Med, Denver, CO USA

[3] Univ Colorado, Dept Pharmaceut Sci, Denver, CO 80202 USA

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2012年 / 355卷 / 01期

关键词：

miRNA; Progestin; Breast cancer; ATP1B1; Progesterone receptor; DNASE FOOTPRINT TITRATION; MICRORNA EXPRESSION; ESTROGEN-RECEPTOR; MAMMARY-GLAND; OVARIAN-STEROIDS; NUCLEAR RECEPTOR; MESSENGER-RNAS; B-ISOFORM; NA; K-ATPASE; ATPASE;

D O I：

10.1016/j.mce.2011.12.020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

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'UTR, 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：15 / 24

页数：10

共 62 条

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