Opposite Roles of the JMJD1A Interaction Partners MDFI and MDFIC in Colorectal Cancer

Sci Rep. 2020 May 26;10(1):8710. doi: 10.1038/s41598-020-65536-6.


MyoD family inhibitor (MDFI) and MDFI domain-containing (MDFIC) are homologous proteins known to regulate myogenic transcription factors. Hitherto, their role in cancer is unknown. We discovered that MDFI is up- and MDFIC downregulated in colorectal tumors. Mirroring these different expression patterns, MDFI stimulated and MDFIC inhibited growth of HCT116 colorectal cancer cells. Further, MDFI and MDFIC interacted with Jumonji C domain-containing (JMJD) 1 A, a histone demethylase and epigenetic regulator involved in colorectal cancer. JMJD1A influenced transcription of several genes that were also regulated by MDFI or MDFIC. Notably, the HIC1 tumor suppressor gene was stimulated by JMJD1A and MDFIC, but not by MDFI, and HIC1 overexpression phenocopied the growth suppressive effects of MDFIC in HCT116 cells. Similar to colorectal cancer, MDFI was up- and MDFIC downregulated in breast, ovarian and prostate cancer, but both were overexpressed in brain, gastric and pancreatic tumors that implies MDFIC to also promote tumorigenesis in certain tissues. Altogether, our data suggest a tumor modulating function for MDFI and MDFIC in colorectal and other cancers that may involve their interaction with JMJD1A and a MDFIC→HIC1 axis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Myogenic Regulatory Factors / metabolism*
  • Sequence Analysis, RNA


  • HIC1 protein, human
  • Kruppel-Like Transcription Factors
  • MDFIC protein, human
  • Myogenic Regulatory Factors
  • MDFI protein, human
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3A protein, human