BTF3-mediated regulation of BMI1 promotes colorectal cancer through influencing epithelial-mesenchymal transition and stem cell-like traits.

The critical roles of transcription factors in cell differentiation and the delineation of cell phenotypes have been reported. The current study aimed to characterize the functions of the basic transcription factor 3 (BTF3) gene and its regulation of the intestinal stem cell marker B cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) gene in colorectal cancer (CRC). Stem cell-like traits and epithelial-mesenchymal transition (EMT) of cultured human CRC cell line HCT116 were evaluated by CD133+ subpopulation counting, colony formation, tumorosphere generation, and expression of EMT-specific markers and stem cell markers. The interaction of BTF3 with BMI1 was analyzed. BTF3 was overexpressed in CRC tissues, which was associated with poor patient survival. BTF3 knockdown impaired the retention of stem cell-like traits of HCT116 and inhibited the EMT of HCT116 cells. BMI1 expression changed in a BTF3-dependent manner, and its overexpression could partially restore stem cell-like traits and EMT of cultured HCT116 cells after BTF3 knockdown. In parallel, treatment with the BMI1 inhibitor PTC-209 mimicked the effects of BTF3 knockdown on stem cell-like traits and EMT of cultured HCT116 cells. Together, these results support the notion that BTF3 and BMI1 are potential therapeutic targets to limit CRC metastasis.