The effects of alternative splicing on miRNA binding sites in bladder cancer

Seonggyun Han, Dongwook Kim, Manu Shivakumar, Young Ji Lee, Tullika Garg, Jason E. Miller, Ju Han Kim, Dokyoon Kim, Younghee Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Eukaryotic organisms have developed a variety of mechanisms to regulate translation post-transcriptionally, including but not limited to the use of miRNA silencing in many species. One method of post-transcriptional regulation is through miRNAs that bind to the 3' UTRs to regulate mRNA abundance and influence protein expression. Therefore, the diversity of mRNA 30 UTRs mediating miRNA binding sites influence miRNA-mediated regulation. Alternative polyadenylation, by shortening mRNA isoforms, increases the diversity of 30 UTRs; moreover, short mRNA isoforms elude miRNA-medicated repression. Because no current prediction methods for putative miRNA target sites consider whether or not 1) splicing-informed miRNA binding sites and/or 2) the use of 30 UTRs provide higher resolution or functionality, we sought to identify not only the genome-wide impact of using exons in mRNA 30 UTRs but also their functional connection to miRNA regulation and clinical outcomes in cancer. With a genome-wide expression of mRNA and miRNA quantified by 395 bladder cancer cases from The Cancer Genome Atlas (TCGA), we 1) demonstrate the diversity of 30 UTRs affecting miRNA efficiency and 2) identify a set of genes clinically associated with mRNA expression in bladder cancer. Knowledge of 30 UTR diversity will not only be a useful addition to current miRNA target prediction algorithms but also enhance the clinical utility of mRNA isoforms in the expression of mRNA in cancer. Thus, variability among cancer patient’s variability in molecular signatures based on these exon usage events in 30 UTR along with miRNAs in bladder cancer may lead to better prognostic/treatment strategies for improved precision medicine.

Original languageEnglish (US)
Article numbere0190708
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • General

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