Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue

作者：Liang Chen, Youhuai Li, Yebo Fu, Peng Jin, Meng-Hsuan Mo, Michael Stamatakos, Christine Teal, Rachel F. Brem, Alexander Stojadinovic, Michael Grinkemeyer, Timothy A. McCaffrey, Yan-Gao Man, Sidney W. Fu · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0054213 · 被引用次数：103 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、Circular RNAs in diseases

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identifi...