Therapeutic Potential of the miRNA-ATM Axis in the Management of Tumor Radioresistance

Cancer Res. 2020 Jan 15;80(2):139-150. doi: 10.1158/0008-5472.CAN-19-1807. Epub 2019 Nov 25.

Abstract

The ataxia-telangiectasia mutated (ATM) protein kinase is widely known for its function as a chief mobilizer of the DNA damage response (DDR) upon DNA double-strand breaks. ATM orchestrates the DDR by modulating the expression of various miRNAs through several mechanisms. On the other hand, a set of miRNAs contribute to tight regulation of ATM by directly targeting the 3'-untranslated region of ATM mRNA. This review addresses the therapeutic application and molecular mechanisms that underlie the intricate interactions between miRNAs and ATM. It also describes therapeutic delivery of miRNAs in different environments such as hypoxic tumor microenvironments.

Publication types

  • Review

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antagomirs / pharmacology
  • Antagomirs / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Cell Hypoxia / genetics
  • Cell Hypoxia / radiation effects
  • Chemoradiotherapy / methods*
  • Combined Modality Therapy / methods
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / genetics*
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / radiation effects

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Antineoplastic Agents
  • MicroRNAs
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins