Mutations in microRNA binding sites of CEP genes involved in cancer

Cell Biochem Biophys. 2014 Dec;70(3):1933-42. doi: 10.1007/s12013-014-0153-8.

Abstract

The CEP genes play a pivotal role in the replication of the cell. CEP family proteins form the major constituents of the centrosome and play a prominent role in centriole biogenesis and in cell replication. Alteration in CEP genes will result in disruption of cell cycle that may in turn cause cancer. In our study, we found that 16 of the CEP genes are a potential target to miRNA that binds to complementary sequences in 3'untranslated regions (UTR) of mRNA and stop them from translation. Single nucleotide polymorphisms (SNPs) occurring naturally in such miRNA binding site can alter the miRNA: mRNA interaction and can significantly alter gene expression. We developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 44 high-confidence SNPs that may impair miRNA target sites in the 3'UTR of 16 genes. Further we performed expression analysis to shed light on the potential tissues that might be affected by mutation, enrichment analysis to find the metabolic functions of the gene, and network analysis to highlight the important interactions of CEP genes with other genes to provide insight that complex network will be disturbed upon mutation. In this study, we explored and prioritised the SNPs in CEP gene which could act as a potential target in centrosome-associated human disease. Our analysis would provide a thoughtful insight to wet lab researches to understand the expression pattern of CEP genes and binding phenomenon of mRNA and miRNA upon mutation, which is responsible for inhibition of translation process at genomic levels.

MeSH terms

  • 3' Untranslated Regions
  • Algorithms
  • Alleles
  • Binding Sites
  • Cell Cycle Proteins / genetics*
  • Databases, Genetic
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Polymorphism, Single Nucleotide

Substances

  • 3' Untranslated Regions
  • Cell Cycle Proteins
  • MicroRNAs