A Radiosensitivity MiRNA Signature Validated by the TCGA Database for Head and Neck Squamous Cell Carcinomas

Oncotarget. 2015 Oct 27;6(33):34649-57. doi: 10.18632/oncotarget.5299.

Abstract

MicroRNA, a class of small non-coding RNAs, play critical roles in the cellular response to DNA damage induced by ionizing irradiation (IR). Growing evidence shows alteration of miRNAs, in response to radiation, controls cellular radiosensitivity in DNA damage response pathways. However, it is less clear about the clinical relevance of miRNA regulation in radiosensitivity. Using an in vitro system, we conducted microarray to identify a miRNA signature to assess radiosensitivity. The data were validated by analyzing available Head and Neck Squamous Cell Carcinoma (HNSCC) samples in the cancer genome atlas (TCGA) database. A total of 27 miRNAs showed differential alteration in response to IR in an Ataxia-Telangiectasia Mutated (ATM) kinase-dependent manner. We validated the list and identified a five miRNA signature that can predict radiation responsiveness in HNSCC. Furthermore, we found that the expression level of ATM in these patients was correlated with the radiation responsiveness. Together, we demonstrate the feasibility of using a miRNA signature to predict the clinical responsiveness of HNSCC radiotherapy.

Keywords: ATM; miRNA; radiosensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / radiotherapy
  • Cell Line, Tumor
  • Databases, Genetic
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • MicroRNAs / analysis*
  • Oligonucleotide Array Sequence Analysis
  • Radiation Tolerance / genetics*
  • Squamous Cell Carcinoma of Head and Neck
  • Transcriptome / genetics*

Substances

  • MicroRNAs
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins