Annexin 1-nuclear factor-κB-microRNA-26a regulatory pathway in the metastasis of non-small cell lung cancer

Thorac Cancer. 2019 Apr;10(4):665-675. doi: 10.1111/1759-7714.12982. Epub 2019 Feb 12.

Abstract

Background: Annexin 1 (ANXA1) expression is associated with the malignant tumor phenotype, making it an attractive therapeutic target. However, little is known about the regulation of ANXA1 in non-small cell lung cancer (NSCLC).

Methods: We investigated the biological roles of ANXA1 in tumor growth, migration, and invasion, and explored the possibility of ANXA1 as a potential therapeutic target for the treatment of NSCLC.

Results: Our findings revealed that ANXA1 enhanced nuclear factor (NF)-κB activation in NSCLC cells by interaction with inhibitor of NF-κB kinase complex subunit, IKKγ. We also found that NF-κB could negatively regulate microRNA (miR)-26a, and miR-26a was regulated through the ANXA1-NF-κB regulatory pathway. NF-κB activation negatively regulated by miR-26a was confirmed in NSCLC.

Conclusion: Together, these results provide evidence of the mechanisms of the ANXA1-NF-κB-miR-26a regulatory pathway in the invasion and migration in NSCLC.

Keywords: Annexin 1; microRNA-26a; non-small cell lung carcinoma; nuclear factor-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Aged
  • Animals
  • Annexin A1 / genetics*
  • Annexin A1 / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • I-kappa B Kinase / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Prognosis
  • Rats
  • Signal Transduction
  • Survival Analysis

Substances

  • ANXA1 protein, human
  • Annexin A1
  • MIRN26A microRNA, human
  • MicroRNAs
  • NF-kappa B
  • I-kappa B Kinase