HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL

Biochem Pharmacol. 2018 Jan;147:30-37. doi: 10.1016/j.bcp.2017.11.008. Epub 2017 Dec 1.


Although histone deacetylase (HDAC) inhibitors have been shown to effectively induce the inhibition of proliferation and migration in breast cancer, the anticancer mechanism remains poorly understood. Our studies show that miR-200c was significantly downregulated in breast cancer cell lines compared to normal cell lines and inversely correlated with the levels of class IIa HDACs and CRKL. HDAC inhibitors and the ectopic expression of miR-200c as tumor suppressors inhibited the proliferation, invasion, and migration of breast cancer cells by downregulating CRKL. These results indicate that the anticancer mechanism of HDAC inhibitor was realized partially by regulating miR-200c via CRKL targeting. Our findings suggest that the HDAC-miR200c-CRKL signaling axis could be a novel diagnostic marker and potential therapeutic target in breast cancer.

Keywords: Breast cancer; CRKL; HDAC inhibitor; MiR-200c; SAHA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Female
  • Gene Targeting
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • CRKL protein
  • Histone Deacetylase Inhibitors
  • MIRN200 microRNA, human
  • MicroRNAs
  • Nuclear Proteins