Expression of versican 3'-untranslated region modulates endogenous microRNA functions
| Autor: | Yaou Zhang, Ling Fang, William W. Du, Jennifer Yang, Minhui Li, Daniel Y. Lee, Albert Y. Yee, Zina Jeyapalan, Tatiana Shatseva, Burton B. Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
lcsh:Medicine
Mice 03 medical and health sciences Versicans 0302 clinical medicine Molecular Biology/Translational Regulation Cell Line Tumor Gene expression microRNA Animals PTEN lcsh:Science 3' Untranslated Regions Cell Proliferation 030304 developmental biology 0303 health sciences Multidisciplinary biology Three prime untranslated region lcsh:R Mammary Neoplasms Experimental Cell Biology Transfection Fibronectin MicroRNAs Oncology/Breast Cancer 030220 oncology & carcinogenesis Molecular Biology/Post-Translational Regulation of Gene Expression Cancer cell biology.protein Cancer research Versican lcsh:Q Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 10, p e13599 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background 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. Methods and Findings 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. Conclusion 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|