Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells
Journal
PLoS ONE
Journal Volume
8
Journal Issue
2
Pages
e56958
Date Issued
2013
Author(s)
Abstract
Alternative polyadenylation (APA) could result in mRNA isoforms with variable lengths of 3′ UTRs. Gain of microRNA target sites in the 3′ UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit a lower ratio of long and short isoforms (LSR); that is, they tend to express larger amounts of short isoforms. The objective of this study is to illustrate the relationship between microRNA differential regulation and LSR. We retrieved public APA annotations and isoform expression profiles of breast cancer and normal cells from a high-throughput sequencing method study specific for the mRNA 3′ end. Combining microRNA expression profiles, we performed statistical analysis to reveal and estimate microRNA regulation on APA patterns in a global scale. First, we found that the amount of microRNA target sites in the alternative UTR (aUTR), the region only present in long isoforms, could affect the LSR of the target genes. Second, we observed that the genes whose aUTRs were targeted by up-regulated microRNAs in cancer cells had an overall lower LSR. Furthermore, the target sites of up-regulated microRNAs tended to appear in aUTRs. Finally, we demonstrated that the amount of target sites for up-regulated microRNAs in aUTRs correlated with the LSR change between cancer and normal cells. The results indicate that up-regulation of microRNAs might cause lower LSRs of target genes in cancer cells through degradation of their long isoforms. Our findings provide evidence of how microRNAs might play a crucial role in APA pattern shifts from normal to cancerous or proliferative states. ? 2013 Liaw et al.
SDGs
Other Subjects
microRNA; RNA isoform; 3' untranslated region; article; breast cancer; cancer growth; cell strain MCF 7; controlled study; down regulation; gene control; gene expression profiling; gene expression regulation; gene function; gene targeting; genetic association; genetic correlation; genetic variability; high throughput sequencing; human; human cell; molecular evolution; molecular pathology; polyadenylation; RNA analysis; RNA degradation; upregulation; 3' Untranslated Regions; Breast Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; MicroRNAs; Polyadenylation; RNA Interference; RNA Isoforms; RNA, Messenger
Publisher
PLoS
Type
journal article