The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis

Genomics. 2015 Jan;105(1):5-16. doi: 10.1016/j.ygeno.2014.10.013. Epub 2014 Nov 13.

Abstract

Previously, we have shown that shortening of telomeres by telomerase inhibition sensitized cancer cells to cisplatinum, slowed their migration, increased DNA damage and impaired DNA repair. The mechanism behind these effects is not fully characterized. Its clarification could facilitate novel therapeutics development and may obviate the time consuming process of telomere shortening achieved by telomerase inhibition. Here we aimed to decipher the microRNA and proteomic profiling of cancer cells with shortened telomeres and identify the key mediators in telomere shortening-induced damage to those cells. Of 870 identified proteins, 98 were differentially expressed in shortened-telomere cells. 47 microRNAs were differentially expressed in these cells; some are implicated in growth arrest or act as oncogene repressors. The obtained data was used for a network construction, which provided us with nodal candidates that may mediate the shortened-telomere dependent features. These proteins' expression was experimentally validated, supporting their potential central role in this system.

Keywords: Cancer cells; Functional networks; Proteomics; Telomeres.

MeSH terms

  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics*
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Oligonucleotides / pharmacology
  • Proteome / analysis*
  • Proteomics
  • Telomere Shortening*
  • Tumor Cells, Cultured

Substances

  • GRN163
  • MicroRNAs
  • Oligonucleotides
  • Proteome