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miR-338-3p在乳腺癌细胞和癌相关成纤维细胞（CAFs）中通过G蛋白偶联雌激素受体（GPER）受雌激素调控。

miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs).

作者信息

Vivacqua Adele, Sebastiani Anna, Miglietta Anna Maria, Rigiracciolo Damiano Cosimo, Cirillo Francesca, Galli Giulia Raffaella, Talia Marianna, Santolla Maria Francesca, Lappano Rosamaria, Giordano Francesca, Panno Maria Luisa, Maggiolini Marcello

机构信息

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.

Regional HospitalCosenza, 87100 Cosenza, Italy.

出版信息

Cells. 2018 Nov 9;7(11):203. doi: 10.3390/cells7110203.

DOI:10.3390/cells7110203
PMID:30423928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6262471/
Abstract

Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

摘要

雌激素通过经典雌激素受体（ERs）和G蛋白雌激素受体（GPER）发挥作用，调控多种微小RNA（miRNAs）的表达，这些非编码RNA短序列参与包括乳腺癌在内的多种病理生理过程。为了深入了解雌激素对乳腺肿瘤中miRNAs的调控机制，我们采用TaqMan芯片技术检测了17β-雌二醇（E2）处理后ER阴性且GPER阳性的SkBr3乳腺癌细胞和癌相关成纤维细胞（CAFs）中754种miRNAs的表达。E2以独特的方式调控SkBr3癌细胞和CAFs中的多种miRNAs，而miR-338-3p在两种细胞类型中表现出相似的调控模式。通过METABRIC数据库分析，我们确定miR-338-3p与乳腺癌患者的总生存期呈正相关，此前的研究表明miR-338-3p可能抑制不同癌细胞的生长和侵袭。与这些数据相符的是，在SkBr3癌细胞和CAFs中，miR-338-3p模拟序列降低了E2通过GPER诱导的基因表达和增殖效应，而miR-338-3p抑制序列则恢复了这种效应。总之，我们的研究结果为E2调控miR-338-3p促进乳腺癌进展的分子机制提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/2a45a921e399/cells-07-00203-g009a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/5ebca991219c/cells-07-00203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/f522fe7e2bee/cells-07-00203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/7737d309e310/cells-07-00203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/205aa76cfecb/cells-07-00203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/3a8b5956c773/cells-07-00203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/89c7fa22a080/cells-07-00203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/792917d72a17/cells-07-00203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/fd2ec2603495/cells-07-00203-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/2a45a921e399/cells-07-00203-g009a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/5ebca991219c/cells-07-00203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/f522fe7e2bee/cells-07-00203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/7737d309e310/cells-07-00203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/205aa76cfecb/cells-07-00203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/3a8b5956c773/cells-07-00203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/89c7fa22a080/cells-07-00203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/792917d72a17/cells-07-00203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/fd2ec2603495/cells-07-00203-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746a/6262471/2a45a921e399/cells-07-00203-g009a.jpg

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