4.5 Article

A non-coding transcript of nephronectin promotes osteoblast differentiation by modulating microRNA functions

Journal

FEBS LETTERS
Volume 585, Issue 16, Pages 2610-2616

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2011.07.016

Keywords

MicroRNA; 3 '-UTR; Nephronectin; Multiplex PCR; Cell differentiation

Funding

  1. Heart and Stroke Foundation of Ontario [NA6732, CI 5958]

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We investigated the roles of the non-coding transcripts and found that expression of a fragment containing the 3'-untranslated region (3'-UTR) of nephronectin in osteoblast progenitor cells MC3T3-E1 promoted cell differentiation dramatically. We hypothesized that the ectopically expressed 3'-UTR binds microRNAs and modulates their functions. beta-Catenin and GSK3 beta were up-regulated in the 3'-UTR-transfected cells, contributing to the increased cell differentiation, through reduction of EGFR and ERK phosphorylation. Activator of GSK3 beta promoted differentiation, while inhibitor of GSK3 beta blocked differentiation. Our results indicate that the non-coding transcripts are important in regulating cell activities and may have potential application for modulating endogenous microRNA functions. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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