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.

MyoD家族抑制剂（MDFI）和含MDFI域的（MDFIC）是已知的调节肌原性转录因子的同源蛋白。迄今为止，它们在癌症中的作用尚不清楚。我们发现在结直肠肿瘤中MDFI被上调，而MDFIC被下调。反映了这些不同的表达方式，MDFI刺激和MDFIC抑制了HCT116大肠癌细胞的生长。此外，MDFI和MDFIC与包含Jumonji C结构域（JMJD）1 A相互作用，后者是参与结直肠癌的组蛋白脱甲基酶和表观遗传调节剂。JMJD1A影响了几个也受MDFI或MDFIC调节的基因的转录。值得注意的是，HIC1肿瘤抑制基因受JMJD1A和MDFIC刺激，但不受MDFI刺激，HIC1过表达显着抑制MDFIC在HCT116细胞中的生长抑制作用。与大肠癌相似，MDFI在乳腺癌，卵巢癌和前列腺癌中上调，而MDFIC下调，但在脑，胃和胰腺肿瘤中均过表达，这表明MDFIC也可促进某些组织的肿瘤发生。总之，我们的数据表明，MDFI和MDFIC在结直肠癌和其他癌症中具有肿瘤调节功能，可能涉及它们与JMJD1A和MDFIC→HIC1轴的相互作用。