NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis

J Cell Physiol. 2024 Sep;239(9):e31345. doi: 10.1002/jcp.31345. Epub 2024 Jun 28.

Abstract

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Keywords: LOX; NAMPT; chondrosarcoma; metastasis; miR‐26b‐5p.

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Chondrosarcoma* / genetics
  • Chondrosarcoma* / metabolism
  • Chondrosarcoma* / pathology
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nicotinamide Phosphoribosyltransferase* / genetics
  • Nicotinamide Phosphoribosyltransferase* / metabolism
  • Protein-Lysine 6-Oxidase* / genetics
  • Protein-Lysine 6-Oxidase* / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Nicotinamide Phosphoribosyltransferase
  • MicroRNAs
  • MIRN26 microRNA, human
  • nicotinamide phosphoribosyltransferase, human
  • Protein-Lysine 6-Oxidase
  • Cytokines
  • LOX protein, human
  • Proto-Oncogene Proteins c-akt