Integrative analysis of somatic mutations altering microRNA targeting in cancer genomes

Jesse D Ziebarth1, Anindya Bhattacharya, Yan Cui

  • 1Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.

Plos One
|October 24, 2012
PubMed

Insights

Somatic mutations in 3' untranslated regions (UTRs) can alter microRNA (miRNA) targeting, affecting gene expression in cancer. This study reveals how these mutations impact miRNA binding sites, potentially driving tumorigenesis.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Biology

Background:

  • Somatic mutations in non-coding regions are increasingly recognized for their role in cancer.
  • Understanding the functional impact of these mutations is key to deciphering tumorigenesis and metastasis.

Purpose of the Study:

  • To investigate the impact of somatic mutations in 3'UTRs on microRNA (miRNA) targeting and gene expression regulation in four cancer types.
  • To identify specific genes and miRNA interactions affected by somatic mutations, and integrate this with germline data and cancer association studies.

Main Methods:

  • Computational prediction of miRNA target site alterations due to somatic mutations in 3'UTRs.
  • Analysis of somatic mutations across four cancer genomes.
  • Integration of somatic mutation data with germline mutations and cancer genome association study results.

Main Results:

  • Somatic mutations were found to create or disrupt putative miRNA target sites in the 3'UTRs of numerous genes, including cancer-associated genes like MITF, EPHA3, TAL1, SCG3, and GSDMA.
  • Specific genes (BMPR1B, KLK3, SPRY4) showed 3'UTR miRNA target sites disrupted by both somatic and germline mutations, linked to cancer association study markers.
  • A somatic mutation in BMPR1B affected a miR-125b target site, mirroring previously observed effects of germline mutations on BMPR1B regulation and cancer linkage.

Conclusions:

  • Somatic mutations in 3'UTRs significantly impact miRNA targeting, offering a mechanism for gene dysregulation in cancer.
  • The interplay between somatic and germline mutations in miRNA binding sites, particularly in genes like BMPR1B, highlights their combined role in cancer development.
  • This research provides insights into the functional consequences of non-coding somatic mutations and their contribution to cancer pathology.

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