Post-transcriptional up-regulation of miR-21 by type I collagen

✍ Scribed by Cui Li; Hong T. Nguyen; Yan Zhuang; Yi Lin; Erik K. Flemington; Weichao Guo; James Guenther; Matthew E. Burow; Gilbert F. Morris; Deborah Sullivan; Bin Shan

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 649 KB
• Volume: 50
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20742

✦ Synopsis

Abstract

Composition of extracellular matrix (ECM) is crucial to the establishment and maintenance of epithelial apical‐basolateral polarity. Increased ECM rigidity caused by deposition of fibrillar collagen, for example, collagen type I (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 explored a link between microRNAs and Col‐1 using organotypic three‐dimensional culture in which epithelial cells are embedded within Matrigel, a mimic of basement membrane matrix (Matrigel 3‐D). Matrigel 3‐D culture of A549, MCF‐7, and mK‐ras‐LE cells (lung and mammary epithelial cell lines) gave rise to acinus, an in vitro equivalent of apical‐basolateral polarity that consists of a polarized monolayer of epithelial cells facing a central lumen. Supplementation of Col‐1 disrupted acinus. Moreover, Col‐1 up‐regulated the expression of miR‐21, a well‐documented oncogenic microRNA, via a post‐transcriptional mechanism. Similar post‐transcriptional up‐regulation of miR‐21 correlated with deposition of Col‐1 in a murine model of lung fibrogenesis. In summary, our findings link 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. Mol. Carcinog. © 2011 Wiley‐Liss, Inc.