MicroRNA-29a Functions as a Tumor Suppressor and Increases Cisplatin Sensitivity by Targeting NRAS in Lung Cancer

Technol Cancer Res Treat. 2018 Jan 1:17:1533033818758905. doi: 10.1177/1533033818758905.

Abstract

MicroRNAs have been reported to play an important role in diverse biological processes and progression of various cancers. MicroRNA-29a has been observed to be downregulated in human lung cancer tissues, but the function of microRNA-29a in lung cancer has not been well investigated. In this study, we demonstrated that the expression levels of microRNA-29a were significantly downregulated in 38 pairs of lung cancer tissues when compared to adjacent normal tissues. Overexpression of microRNA-29a inhibited the activity of cell proliferation and colony formation of lung cancer cells, H1299 and A549. Furthermore, microRNA-29a targeted NRAS proto-oncogene in lung cancer cells. In human clinical specimens, NRAS proto-oncogene was highly expressed in human lung cancer tissues compared to normal tissues. More interestingly, microRNA-29a also sensitizes lung cancer cells to cisplatin (CDDP[Please replace "CDDP" with its expansion in the abstract and also provide expansion for the same in its first occurrence in text, if appropriate.]) via its target, NRAS proto-oncogene. Thus, our results in this study demonstrated that microRNA-29a acted as a tumor suppressor microRNA, which indicated potential application of microRNAs for the treatment of human lung cancer in the future.

Keywords: NRAS; cisplatin; lung cancer; miR-29a; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • GTP Phosphohydrolases / biosynthesis*
  • GTP Phosphohydrolases / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Mas

Substances

  • Antineoplastic Agents
  • MAS1 protein, human
  • MIRN29a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Mas
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Cisplatin