Identification of MicroRNA-Related Tumorigenesis Variants and Genes in the Cancer Genome Atlas (TCGA) Data.

Chang Li,Xiaoming Liu,Brian Wu,Han Han,Jeff Zhao,Yongsheng Bai

doi:10.3390/genes11090953

Chang Li, Xiaoming Liu + Show 4 more

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https://doi.org/10.3390/genes11090953

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Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNA that can down-regulate their targets by selectively binding to the 3′ untranslated region (3′UTR) of most messenger RNAs (mRNAs) in the human genome. Single nucleotide variants (SNVs) located in miRNA target sites (MTS) can disrupt the binding of targeting miRNAs. Anti-correlated miRNA–mRNA pairs between normal and tumor tissues obtained from The Cancer Genome Atlas (TCGA) can reveal important information behind these SNVs on MTS and their associated oncogenesis. In this study, using previously identified anti-correlated miRNA–mRNA pairs in 15 TCGA cancer types and publicly available variant annotation databases, namely dbNSFP (database for nonsynonymous SNPs’ functional predictions) and dbMTS (database of miRNA target site SNVs), we identified multiple functional variants and their gene products that could be associated with various types of cancers. We found two genes from dbMTS and 33 from dbNSFP that passed our stringent filtering criteria (e.g., pathogenicity). Specifically, from dbMTS, we identified 23 candidate genes, two of which (BMPR1A and XIAP) were associated with diseases that increased the risk of cancer in patients. From dbNSFP, we identified 65 variants located in 33 genes that were likely pathogenic and had a potential causative relationship with cancer. This study provides a novel way of utilizing TCGA data and integrating multiple publicly available databases to explore cancer genomics.

Highlights

MicroRNAs are small (21–22bp) noncoding RNAs that play a post-transcriptional regulatory role through targeting the 30 untranslated regions (UTRs) of messenger RNAs (mRNAs)(s)
Because miRNA can repress the expression of its targets, we hypothesize that these anti-correlated miRNA–mRNA pairs are likely to be dysregulated in the observed cancer types, which highlight their potential functional importance
One piece of important information in dbMTS that we considered was the name of the miRNA–mRNA pair that was disrupted or created by introducing the Single nucleotide variants (SNVs)

Summary

Introduction

MicroRNAs (miRNA) are small (21–22bp) noncoding RNAs that play a post-transcriptional regulatory role through targeting the 30 untranslated regions (UTRs) of mRNA(s). MiRNAs regulate mRNA(s) via base pairing through complementary sequences within mRNA molecules. Especially Single Nucleotide Variants (SNVs) located on the miRNA target site (MTS), can disrupt the binding of targeting miRNAs. Genetic mutations, especially Single Nucleotide Variants (SNVs) located on the miRNA target site (MTS), can disrupt the binding of targeting miRNAs This disruption has been reported to be associated with numerous diseases and cancers [1]. Given their functional importance, our understanding of the role of MTS SNVs towards cancer is very limited, and many such SNVs have not even been identified.

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