miR-4732-3p prevents lung cancer progression via inhibition of the TBX15/TNFSF11 axis

Epigenomics. 2023 Feb;15(4):195-207. doi: 10.2217/epi-2023-0009. Epub 2023 Apr 26.

Abstract

Aim: Possible roles of miRNAs in cancer treatment have been highly studied. This study aimed to elucidate the role of miR-4732-3p in lung cancer. Methods: Bioinformatics analysis was conducted to predict miR-4732-3p-related mRNA targets in lung cancer. Following interaction determination between miR-4732-3p and TBX15 as well as between TBX15 and TNFSF11, their in vitro and in vivo roles were assayed. Results: miR-4732-3p negatively targeted TBX15, which upregulated TNFSF11 by enhancing the activity of the TNFSF11 promoter. Overexpression of miR-4732-3p or silencing of TBX15 or TNFSF11 inhibited the malignant phenotype of lung cancer cells and reduced tumorigenicity in vivo. Conclusion: Overall, this study highlighted the inhibitory role of miR-4732-3p in lung cancer progression through the TBX15/TNFSF11 axis.

Keywords: TBX15; TNFSF11; invasion; lung cancer; miR-4732-3p; migration; proliferation; promoter activity.

Plain language summary

This study describes the role of miR-4732-3p in lung cancer. The authors conducted bioinformatics analysis to predict miR-4732-3p-related mRNA targets in lung cancer. Then they analyzed the potential interaction between miR-4732-3p and TBX15 and between TBX15 and TNFSF11. To evaluate their effects on the progression of lung cancer, the authors performed in vitro and in vivo assays. They discovered that miR-4732-3p negatively targeted TBX15, which upregulated TNFSF11 by enhancing the activity of TNFSF11 promoter. Overexpression of miR-4732-3p or silencing of TBX15 or TNFSF11 inhibited the malignant phenotype of lung cancer cells and reduced tumorigenicity in vivo. This study, which has identified potential for the miR-4732-3p/TBX15/TNFSF11 axis as an antioncogenic tool, opens the possibility for better monitoring of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Computational Biology
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Phenotype
  • Promoter Regions, Genetic
  • RANK Ligand
  • T-Box Domain Proteins / genetics

Substances

  • MicroRNAs
  • RANK Ligand
  • T-Box Domain Proteins
  • TBX15 protein, human
  • TNFSF11 protein, human
  • MIRN4732 microRNA, human