Deregulated miRNA in Mammary Epithelium by Tumor Promoting Extracellular Matrix
Abstract
The goal of this project is to identify the miRNAs that are altered by the aberrant extracellular matrix within the tumor microenvironment, particularly the fibrillary collagen, Collagen type I (Col-1). The biochemical and biophysical properties of the extracellular matrix (ECM) are essential to the establishment and maintenance of epithelial polarity. Increased ECM rigidity caused by deposition of fibrillar collagen, e.g., type I collagen (Col-1), promotes loss of epithelial polarity and tumor progression. microRNAs are small non-coding RNAs that regulate gene expression and fundamental cellular processes. The current study explores a link between microRNAs and Col-1 deposition using organotypic three-dimensional culture in which epithelial cells are embedded within Matrigel, a mimic of basement membrane matrix (rBM 3-D). rBM 3-D culture of MCF-7 gave rise to acini that consisted of a polarized monolayer of epithelial cells facing a central lumen, an in vitro phenomenon of epithelial polarity. Supplementation of Col-1 disrupted acini and up-regulated the expression of miR-21, a well-documented oncogenic microRNA, via a post-transcriptional mechanism, which correlates with a decrease in two miR-21 targets, programmed cell death 4 and phosphatase and tensin homologue. In summary, our findings provide a link between altered ECM composition/rigidity and the expression of oncogenic microRNAs. The current study also suggests a novel post-transcriptional mechanism for regulation of miR-21 expression at maturation from pre-miR-21 to mature miR-21. We also compared the expression of miRNAs in rBM 3-D and 2-D cultures of the noninvasive MCF-7 and the invasive MDA-MB231 cells. Our findings revealed a profound difference in miRNA profiles between 2-D and rBM 3-D cultures within each cell type. The disparate miRNA profiles correlated with distinct mass morphogenesis of MCF-7 and invasive stellate morphogenesis of MDA-MB231 cells in rBM 3-D culture.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA587722
Entities
People
- Bin Shan
Organizations
- Tulane University of Louisiana