Visfatin-Induced Inhibition of miR-1264 Facilitates PDGF-C Synthesis in Chondrosarcoma Cells and Enhances Endothelial Progenitor Cell Angiogenesis

Cells. 2022 Nov 2;11(21):3470. doi: 10.3390/cells11213470.

Abstract

New treatments for chondrosarcoma are extremely important. Chondrosarcoma is a primary malignant bone tumor with a very unfavorable prognosis. High-grade chondrosarcoma has a high potential to metastasize to any organ in the body. Platelet-derived growth factor (PDGF) is a potent angiogenic factor that promotes tumor angiogenesis and metastasis. The adipocytokine visfatin promotes metastatic potential of chondrosarcoma; however, the role of visfatin in angiogenesis in human chondrosarcoma is unclear. We report that the levels of PDGF-C expression were positively correlated with tumor stages, significantly higher than the levels of expression in normal cartilage. Visfatin increased PDGF-C expression and endothelial progenitor cell (EPC) angiogenesis through the PI3K/Akt/mTOR signaling pathway, and dose-dependently down-regulated the synthesis of miR-1264, which targets the 3'-UTR of PDGF-C. Additionally, we discovered inhibition of visfatin or PDGF-C in chondrosarcoma tumors significantly reduced tumor angiogenesis and size. Our results indicate that visfatin inhibits miR-1264 production through the PI3K/Akt/mTOR signaling cascade, and thereby promotes PDGF-C expression and chondrosarcoma angiogenesis. Visfatin may be worth targeting in the treatment of chondrosarcoma angiogenesis.

Keywords: PDGF-C; angiogenesis; chondrosarcoma; endothelial progenitor cell; platelet-derived growth factor; tumor angiogenesis; visfatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms* / metabolism
  • Chondrosarcoma* / metabolism
  • Endothelial Progenitor Cells* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neovascularization, Pathologic / metabolism
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • platelet-derived growth factor C
  • Nicotinamide Phosphoribosyltransferase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Vascular Endothelial Growth Factor A
  • Platelet-Derived Growth Factor
  • TOR Serine-Threonine Kinases
  • MicroRNAs

Grants and funding

This work was supported by a grant from [the Ministry of Science and Technology of Taiwan], grant number [MOST 108-2314-B-039-034-MY3; MOST 111-2314-B-039-048-MY3; MOST 110-2320-B-039-022-MY3]. [China Medical University], grant number [CMU110-ASIA-02] and [China Medical University Hospital], grant number [DMR-111-108; DMR-111-229; DMR-111-235].