Microglial Annexin A3 promoted the development of melanoma via activation of hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway

J Clin Lab Anal. 2021 Feb;35(2):e23622. doi: 10.1002/jcla.23622. Epub 2020 Oct 29.

Abstract

Background: Melanoma, a relatively common malignancy, has become one of the tumors with the fastest rising incidence in recent years. The purpose of this study was to investigate the effect of Microglial Annexin A3 (ANXA3) on melanoma.

Methods: Serum samples were obtained from 20 patients with melanoma or 20 healthy controls. Kaplan-Meier survival analysis was performed. Transcriptome were used to analyze the correlation between ANXA3 expression and overall survival in patients with melanoma. Human melanoma cell lines WM-115 cells were transfected with ANXA3, si-ANXA3, ANXA3 + si-hypoxia inducible factor-1α (HIF-1α), si-ANXA3 + HIF-1α, and negative plasmids. Cell proliferation assay, cell invasion assay, and wound healing assay were performed on WM-115 cells. Lactate dehydrogenase (LDH) and caspase-3/9 activities were detected by commercial kits. Western blot and RT-PCR were used to detect the protein and mRNA expression of relation factors.

Results: ANXA3 expression was up-regulated in patients with melanoma in comparison with healthy controls. Over-expression of ANXA3 promoted cell growth and migration, and reduced cytotoxicity of WM-115 cells. Overall survival (OS) and disease-free survival (DFS) of patients with high ANXA3 expression were both lower than those of patients with low ANXA3 expression. Down-regulation of ANXA3 reduced cell growth and migration, and promoted cytotoxicity of WM-115 cells. ANXA3 induced vascular endothelial growth factor (VEGF) signaling pathway by activation of HIF-1α.

Conclusion: In conclusion, our results indicated that ANXA3 promoted cell growth and migration of melanoma via activation of HIF-1α/VEGF signaling pathway.

Keywords: ANXA3; HIF-1α; VEGF; cell growth; melanoma; migration.

MeSH terms

  • Annexin A3 / blood
  • Annexin A3 / genetics
  • Annexin A3 / metabolism*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Melanoma / pathology*
  • Melanoma, Cutaneous Malignant
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • ANXA3 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Annexin A3