IL-1β-induced NF-κB activation down-regulates miR-506 expression to promotes osteosarcoma cell growth through JAG1

Biomed Pharmacother. 2017 Nov;95:1147-1155. doi: 10.1016/j.biopha.2017.08.120. Epub 2017 Oct 6.

Abstract

Nowadays, the role of miRNA in tumorigenesis has been largely reported. It was found that miR-506 might be associated with tumorigenesis of various cancers. The present study was aimed to investigate the character of miR-506 and some related factors in human osteosarcoma (OS) carcinogenesis. The expression level of miR-506 was downregulated in OS compared with the normal control group by RT-PCR, both in vivo and in vitro. In addition, IL-1β stimulation decreased the expression of miR-506. MiR-506 interfered with JAG1 gene transcription throughmiR-506 binding to the 3'-UTR region of JAG1 gene. Further siRNA strategy suggested that IL-1β may regulate miR-506 level via NF-κB, and then alter the JAG1 expression. Besides, the suppression of JAG1 by miR-506 inhibited OS cell proliferation. Taken together, our data indicate a process of NF-κB-induced miR-506 suppression and JAG1 upregulation upon IL-1β induction, which can be regarded as a new pathway for modulating cell proliferation via miR-506. It may be of clinical value in treating OS in the future.

Keywords: IL-1β; JAG1; NF-κB; Osteosarcoma; miR-506.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-1beta / pharmacology*
  • Jagged-1 Protein / genetics
  • Jagged-1 Protein / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*

Substances

  • 3' Untranslated Regions
  • Interleukin-1beta
  • JAG1 protein, human
  • Jagged-1 Protein
  • MIRN506 microRNA, human
  • MicroRNAs
  • NF-kappa B