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Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics

Mayakannan Manikandan1, Arasambattu Kannan Munirajan

  • 1Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras , Taramani Campus, Chennai, Tamil Nadu, India .

Omics : a Journal of Integrative Biology
|November 30, 2013
PubMed

Insights

Single Nucleotide Polymorphisms (SNPs) in microRNA binding sites of proto-oncogenes may disrupt cancer gene regulation. This can lead to tumor development and affect patient drug response.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Genetics

Background:

  • Cancer is a genetic disease driven by altered oncogene and tumor suppressor gene activity.
  • MicroRNAs (miRNAs) regulate gene expression by binding to messenger RNA (mRNA) 3' untranslated regions (UTRs).
  • Single Nucleotide Polymorphisms (SNPs) in miRNA binding sites can disrupt this regulation.

Purpose of the Study:

  • To investigate how 3'UTR SNPs in proto-oncogene miRNA binding sites affect gene regulation in cancer.
  • To identify specific SNPs that may influence cancer initiation, progression, and drug response.

Main Methods:

  • Developed a computational pipeline integrating multiple databases.
  • Applied stringent selection criteria to identify high-confidence SNPs.
  • Analyzed 54 mRNA transcripts from 24 proto-oncogenes.

Main Results:

  • Identified 30 high-confidence SNPs potentially impairing miRNA target sites in proto-oncogene 3'UTRs.
  • Highlighted 8 SNPs with potential to predict therapeutic outcomes in cancer patients.
  • Found these SNPs predominantly in proto-oncogenes with kinase activity.

Conclusions:

  • 3'UTR SNPs in proto-oncogenes can potentially abrogate miRNA-mediated post-transcriptional regulation.
  • These genetic variations may contribute to cancer development and influence treatment efficacy.
  • In silico analysis provides evidence for the functional impact of these SNPs across various cancers.

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