Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway

Biomed Pharmacother. 2019 Jan:109:2335-2341. doi: 10.1016/j.biopha.2018.11.026. Epub 2018 Nov 29.

Abstract

MicroRNA (miRNA) is known to be involved in regulating the proliferation, migration and apoptosis of cancer cells in osteosarcoma. In this study, We aim to explore the expression of hsa-let-7 g and its role in pathogenesis of osteosarcoma. By analyzing clinical data. We found high expression of hsa-let-7 g in patients with osteosarcoma. The patients with higher expression of hsa-let-7 g showed poorer prognosis and lower survival rate. After downregulation of hsa-let-7 g in cell model and animal model, we found that with downregulation of hsa-let-7 g, the proliferation of osteosarcoma cells was significantly reduced, the level of migration and invasion was down-regulated, the cell cycle was inhibited, and cell apoptosis was increased. Through Dual Luciferase Reporter, immunohistochemistry, western blot and other experiments, it was found that hsa-let-7 g down-regulated HOXB1 gene and activated NF-kB pathway to promote the development of osteosarcoma. In conclusion, hsa-let-7 g is highly expressed in osteosarcoma tissues, and high expression of hsa-let-7 g can promote the occurrence of osteosarcoma by down-regulating HOXB1 and activating NF-kB pathway.

Keywords: HOXB1; Metastasis; NF-kB; Osteosarcoma; microRNAs.

MeSH terms

  • Adolescent
  • Animals
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Female
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • NF-kappa B / metabolism*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • HOXB1 homeodomain protein
  • Homeodomain Proteins
  • MicroRNAs
  • NF-kappa B
  • mirnlet7 microRNA, human