miR-101 promotes breast cancer cell apoptosis by targeting Janus kinase 2

Cell Physiol Biochem. 2014;34(2):413-22. doi: 10.1159/000363010. Epub 2014 Jul 11.

Abstract

Aims: microRNA-101 (miR-101) is down-regulated in several cancers. In this study, we explored the effects of dysregulated miR-101 on breast cancer cells and the underlying mechanisms.

Methods: miR-101 level was quantified by real-time RT-PCR. Cell viability was analyzed by MTT assay. Apoptosis was detected by flow cytometry and TUNEL assay. Moreover, the level of protein expression was determined by Western blot.

Results: miR-101 level was markedly reduced in both the human breast cancer samples and cultured breast cancer cell lines (MCF-7, MDA-MB-231). Overexpression of miR-101 inhibited the proliferation and promoted the apoptosis in cultured MCF-7 and MDA-MB-231 cells, which were reversed by co-transfection of AMO-101, the inhibitor of miR-101. We validated Janus kinase 2 (Jak2) as a direct target of miR-101. Knockdown of Jak2 induced apoptosis in cultured breast cancer cells. Moreover, the level of miR-101 is negatively correlated with Jak2 in breast cancer tissues and cell lines.

Conclusions: miR-101 suppressed proliferation and promoted apoptosis in breast cancer cells by targeting Jak2. These findings indicate that manipulation of miR-101 expression may represent a novel therapeutic strategy in the treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Blotting, Western
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Janus Kinase 2 / genetics*
  • MicroRNAs / physiology*
  • Real-Time Polymerase Chain Reaction

Substances

  • MIRN101 microRNA, human
  • MicroRNAs
  • Janus Kinase 2