Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3

Tumour Biol. 2018 Jan;40(1):1010428317731369. doi: 10.1177/1010428317731369.

Abstract

The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma. Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine kinase, while its effects on multiple myeloma have not been well described. Here, we show that microRNA-21 is an oncogenic marker closely linked with progression of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in multiple myeloma cells by inhibiting nuclear factor-κB and signal transducer and activator of transcription 3 signaling pathways. Taken together, our results suggest that ibrutinib is a promising potential treatment for multiple myeloma. Further investigation of mechanisms of ibrutinib function in multiple myeloma will be necessary to evaluate its use as a novel multiple myeloma treatment.

Keywords: Ibrutinib; microRNA-21; multiple myeloma; nuclear factor-κB; signal transducer and activator of transcription 3.

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • NF-kappa B / metabolism*
  • Piperidines
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • STAT3 Transcription Factor / metabolism*

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • STAT3 Transcription Factor
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Adenine