Androgen Receptor Promotes Lung Cancer Metastasis by Modifying the miR23a-3p/EPHB2 Pathway

Curr Med Sci. 2024 Oct;44(5):954-963. doi: 10.1007/s11596-024-2891-1. Epub 2024 Oct 11.

Abstract

Objective: This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.

Methods: Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models.

Results: The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR.

Conclusion: This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.

Keywords: EPHB2; androgen receptor; lung cancer metastasis; miRNA-23a-3p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • Receptor, EphB2* / genetics
  • Receptor, EphB2* / metabolism
  • Receptors, Androgen* / genetics
  • Receptors, Androgen* / metabolism
  • Signal Transduction* / genetics

Substances

  • MicroRNAs
  • Receptors, Androgen
  • Receptor, EphB2
  • MIRN23a microRNA, human
  • EPHB2 protein, human
  • AR protein, human