Expression of Versican 3′-Untranslated Region Modulates Endogenous MicroRNA Functions
Open Access
- 25 October 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (10), e13599
- https://doi.org/10.1371/journal.pone.0013599
Abstract
Mature microRNAs (miRNAs) are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3′UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3′UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3′UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3′UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3′UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3′UTR formed smaller tumors compared with cells transfected with a control vector. Our results demonstrated that a 3′UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3′UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities.Keywords
This publication has 50 references indexed in Scilit:
- MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8Oncogene, 2010
- Repression of Versican Expression by MicroRNA-143Journal of Biological Chemistry, 2010
- Transforming growth factor‐β inhibits nephronectin‐induced osteoblast differentiationFEBS Letters, 2010
- Nephronectin promotes osteoblast differentiation via the epidermal growth factor‐like repeatsFEBS Letters, 2009
- Microrna-221 and Microrna-222 Modulate Differentiation and Maturation of Skeletal Muscle CellsPLOS ONE, 2009
- MicroRNA miR-378 Regulates Nephronectin Expression Modulating Osteoblast Differentiation by Targeting GalNT-7PLOS ONE, 2009
- Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryosNucleic Acids Research, 2006
- LNA-modified oligonucleotides mediate specific inhibition of microRNA functionGene, 2006
- Silencing of microRNAs in vivo with ‘antagomirs’Nature, 2005
- Regulation by let-7 and lin-4 miRNAs Results in Target mRNA DegradationCell, 2005