The Critical Function of microRNAs in Developing Resistance against 5- Fluorouracil in Cancer Cells

Mini Rev Med Chem. 2024;24(6):601-617. doi: 10.2174/1389557523666230825144150.

Abstract

Although there have been significant advancements in cancer treatment, resistance and recurrence in patients make it one of the leading causes of death worldwide. 5-fluorouracil (5-FU), an antimetabolite agent, is widely used in treating a broad range of human malignancies. The cytotoxic effects of 5-FU are mediated by the inhibition of thymidylate synthase (TYMS/TS), resulting in the suppression of essential biosynthetic activity, as well as the misincorporation of its metabolites into RNA and DNA. Despite its huge benefits in cancer therapy, the application of 5-FU in the clinic is restricted due to the occurrence of drug resistance. MicroRNAs (miRNAs) are small, non-coding RNAs that act as negative regulators in many gene expression processes. Research has shown that changes in miRNA play a role in cancer progression and drug resistance. This review examines the role of miRNAs in 5-FU drug resistance in cancers.

Keywords: 5-FU; Drug resistance; apoptosis; cancer treatment.; chemosensitivity; miRNAs.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic* / pharmacology
  • Drug Resistance, Neoplasm* / drug effects
  • Fluorouracil* / pharmacology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Thymidylate Synthase / antagonists & inhibitors
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism

Substances

  • Fluorouracil
  • MicroRNAs
  • Antimetabolites, Antineoplastic
  • Thymidylate Synthase