The role and mechanisms of action of microRNAs in cancer drug resistance

Clin Epigenetics. 2019 Feb 11;11(1):25. doi: 10.1186/s13148-018-0587-8.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified drug targets, altered cell cycle checkpoints, or increased DNA damage repair, among others. In recent years, many studies have shown that miRNAs are involved in the drug resistance of tumor cells by targeting drug-resistance-related genes or influencing genes related to cell proliferation, cell cycle, and apoptosis. A single miRNA often targets a number of genes, and its regulatory effect is tissue-specific. In this review, we emphasize the miRNAs that are involved in the regulation of drug resistance among different cancers and probe the mechanisms of the deregulated expression of miRNAs. The molecular targets of miRNAs and their underlying signaling pathways are also explored comprehensively. A holistic understanding of the functions of miRNAs in drug resistance will help us develop better strategies to regulate them efficiently and will finally pave the way toward better translation of miRNAs into clinics, developing them into a promising approach in cancer therapy.

Keywords: Cancer; Chemotherapy; Drug resistance; Dysregulation; Mechanisms; MicroRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cell Proliferation
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm*
  • Epigenesis, Genetic
  • Gene Amplification
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Organ Specificity

Substances

  • Antineoplastic Agents
  • MicroRNAs