Deciphering the role of KRAS gene in oncogenesis: Focus on signaling pathways, genetic alterations in 3'UTR, KRAS specific miRNAs and therapeutic interventions

Crit Rev Oncol Hematol. 2024 Feb:194:104250. doi: 10.1016/j.critrevonc.2023.104250. Epub 2023 Dec 22.

Abstract

Cancer is a significant cause of death after cardiovascular disease. The genomic, epigenetic and environmental factors have been found to be the risk factor for the disease. The most important genes that develop cancer are oncogenes and tumor suppressor genes. Among oncogenes, KRAS has emerged as a significant player in the development of many cancers. Dysregulation of the RAS signaling pathway either on account of mutation in significant genes involved in the pathway or aberrant expression of different miRNAs targeting these genes including KRAS. The focus is also on the alterations in 3'UTR of the KRAS gene sequence as well as the changes in the miRNA encoding genes especially the one targeting the KRAS gene. Efforts are also being put in to target the dysregulated KRAS gene as a therapeutic approach to treat different cancers. However, there are some challenges like resistance to KRAS inhibitors that need to be addressed.

Keywords: Cancer; KRAS; MiRNA; Signaling pathways; Therapeutic strategies.

Publication types

  • Review

MeSH terms

  • 3' Untranslated Regions
  • Carcinogenesis / genetics
  • Cell Transformation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • Mutation
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • 3' Untranslated Regions
  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human