Targeting the microRNA-regulating DNA damage/repair pathways in cancer

Maintenance of genome stability requires the integrity of the DNA repair machinery. DNA damage response (DDR) determines cell fate and regulates the expression of microRNAs (miRNAs), which in turn may also regulate important components of the DNA repair machinery.

In this review, we describe the bidirectional connection between miRNAs and DDR and their link with important biological functions such as, DNA repair, cell cycle and apoptosis in cancer. Furthermore, we highlight the potential implications of recent findings on miRNA/DDR in determining chemotherapy response in cancer patients, and the use of these biomarkers for novel potential therapeutic approaches.

Defects in the DDR and deregulation of miRNAs are important hallmarks of human cancer. A full understanding of the mechanisms underlying the connection between miRNAs and DDR/DNA repair pathways will positively impact our knowledge on human tumor biology and on different responses to distinct drugs. Specific miRNAs interact with distinct DDR components and are promising targets for enhancing the effects of, and/or to overcome the resistance to, conventional chemotherapeutic agents. Finally, the development of innovative tools to deliver miRNA-targeting oligonucleotides may represents novel types of cancer interventions in clinic.