title: Post-transcriptional up-regulation of miR-21 by type I collagen.
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.
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Erik K
authors.initials: EK
authors.lastname: Flemington
authors.forename: Weichao
authors.initials: W
authors.lastname: Guo
authors.forename: James
authors.initials: J
authors.lastname: Guenther
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.forename: Gilbert F
authors.initials: GF
authors.lastname: Morris
authors.forename: Deborah
authors.initials: D
authors.lastname: Sullivan
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000502:physiology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; C524940:MIRN21 microRNA, human; D035683:MicroRNAs