MicroRNA-204 targets JAK2 in breast cancer and induces cell apoptosis through the STAT3/BCl-2/survivin pathway

Int J Clin Exp Pathol. 2015 May 1;8(5):5017-25. eCollection 2015.

Abstract

MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-204 plays an important role in various human cancers. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated that miR-204 expression level was markedly reduced in both the human breast cancer tissue and cultured breast cancer cell lines (MCF-7, MDA-MB-231). Overexpression of miR-204 inhibited the proliferation and promoted the apoptosis in breast cancer cells, which were reversed by co-transfection of miR-204 inhibitor. We validated that Janus kinase 2 (JAK2), as a direct target of miR-204, is overexpressed in breast cancer. Knockdown of JAK2 suppressed cell viability and induced apoptosis in breast cancer cells. Moreover, the level of miR-204 is negatively correlated with p-STAT3 and anti-apoptotic genes BCl-2 and surviving in breast cancer. In conclusions, miR-204 targets JAK2 and suppressed JAK2 and p-JAK2 expression in breast cancer, which further inhibit the activation of STAT3, BCl-2 and survivin. These findings indicate that manipulation of miR-204 expression may represent a novel therapeutic strategy in the treatment of breast cancer.

Keywords: Breast cancer; JAK2; apoptosis; miR-204; proliferation.

MeSH terms

  • Apoptosis*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism*
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA Interference
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Survivin
  • Time Factors
  • Transfection

Substances

  • BCL2 protein, human
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • MIRN204 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • JAK2 protein, human
  • Janus Kinase 2