MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4

BMC Cancer. 2018 Jun 4;18(1):631. doi: 10.1186/s12885-018-4460-0.

Abstract

Background: MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer.

Methods: We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance.

Results: The AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells.

Conclusions: Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance.

Keywords: AK4; Multi-chemoresistance; Osteosarcoma; miR-199a-3p.

MeSH terms

  • Adenylate Kinase / genetics*
  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*

Substances

  • MicroRNAs
  • mirn199 microRNA, human
  • Adenylate Kinase