DNA damage response regulation by microRNAs as a therapeutic target in cancer

DNA Repair (Amst). 2016 Nov;47:1-11. doi: 10.1016/j.dnarep.2016.09.003. Epub 2016 Sep 27.

Abstract

The inability of cancer cells in taking care of DNA damages can lead to cancer development and/or progression. Due to the essential role of DNA repair in maintaining genomic stability, tightly controlled regulatory mechanism are required for these processes. Recent studies have shown a myriad of interactions among DNA damage response (DDR) components and miRNAs. While DDR modulates miRNA expression in transcriptional and post-transcriptional levels and affects miRNA degradation, miRNAs in turn, directly modulate the expression of multiple proteins in the DDR pathways, or indirectly fine-tune the expression of such proteins. A better understanding of DDR-miRNA interactions can facilitate the development of new anticancer agents targeting miRNAs involved in the DNA repair process. In this review, we provide a brief introduction about miRNA biogenesis and functions, DDR pathways, and recent findings about DDR-microRNA interactions. Finally, the therapeutic importance of miRNAs in modulation of DDR/DNA repair mechanisms will be discussed.

Keywords: Cancer; Chemotherapy; DNA damage response; DNA repair; microRNA.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • DNA Damage
  • DNA Repair / drug effects*
  • DNA, Neoplasm / genetics*
  • DNA, Neoplasm / metabolism
  • Genome, Human
  • Genomic Instability
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Platinum Compounds / therapeutic use
  • RNA, Neoplasm / antagonists & inhibitors*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Taxoids / therapeutic use
  • Transcription, Genetic

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • DNA, Neoplasm
  • MicroRNAs
  • Neoplasm Proteins
  • Platinum Compounds
  • RNA, Neoplasm
  • Taxoids