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Co-localized genomic regulation of miRNA and mRNA via DNA methylation affects survival in multiple tumor types

James D Doecke1, Ying Wang2, Keith Baggerly2

  • 1Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA; Commonwealth Scientific and Industrial Research Organization (CSIRO) Health and Biosecurity/Australian E-Health Research Centre, Royal Brisbane and Women's Hospital, Level 5, UQ Health Sciences Building, 901/16, Herston, Queensland 4029, Australia.

Cancer Genetics
|November 5, 2016
PubMed

Insights

Aberrant gene expression in cancer involves DNA methylation and microRNA (miRNA) regulation. This study identified genomic "triplet combinations" linking DNA methylation, miRNA, and mRNA, revealing patterns associated with cancer patient survival.

Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Aberrant gene expression in cancer is linked to irregular DNA methylation and microRNA (miRNA) target gene downregulation.
  • Understanding these regulatory mechanisms is crucial for cancer research.

Purpose of the Study:

  • To investigate co-localized mRNA, miRNA, and DNA methylation data across 15 cancer types.
  • To identify genomic regulatory patterns associated with cancer outcomes.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) data for 2839 samples.
  • Analyzed correlations (>0.6) between mRNA, miRNA, and DNA methylation probes within co-localized genomic regions.
  • Identified 180 "triplet combinations" indicating co-localized genomic regulation.

Main Results:

  • Identified 32 genes, 34 miRNAs, and 143 DNA methylation sites forming 180 triplet combinations.
  • HOXC5, PDE2A, SH3TC2, and TP63 showed high prevalence of these combinations.
  • Eight genes were significantly associated with survival in Kidney Renal Clear Cell Carcinoma and Low Grade Glioma.

Conclusions:

  • Data support the hypothesis that genes and miRNAs strongly correlated with DNA methylation levels are associated with cancer outcomes.
  • Identified specific regulatory triplets and genes linked to cancer survival, offering potential biomarkers.
Keywords:
CancerDNA methylationSurvivalmRNAmiRNA

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