CBFß promotes colorectal tumor growth and metastasis in a RUNX2-dependent manner (RNA-seq)
Transcriptional regulation is critically involved in colorectal cancer (CRC) pathogenesis, the mechanism of which remains incompletely understood. Here, we report that core-binding factor ß (CBFß) is commonly upregulated in human colorectal cancer and is associated with the survival rate of CRC patients. Immunohistochemistry (IHC) analysis of RUNX1-3 expression in CRC patients and other in vitro data revealed that CBFß promotes cell proliferation and liver metastasis in a RUNX2-dependent way. Transcriptome sequencing, ChIP-seq and promoter-binding experiments demonstrated that the CBFß/RUNX2 complex could activate the transcription of OPN, FAM129A and UPP1. Furthermore, CBFß significantly promoted tumor growth and lung metastasis in a mouse xenograft model and an orthotopic liver metastasis model of CRC.  Additionally, we identified that tumor-suppressive miR-143/145 could synergistically target CBFß by specifically binding to its 3'-UTR region. An inverse correlation between miR-143/145 and CBFß was verified in CRC patients. Our results represent the first report describing a mechanistic role for CBFß-RUNX2 in the transcriptional activation of OPN, FAM129A and UPP1 in controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities. Overall design: Significantly changed genes both in CBFß-LV-HCT116 cells compared to the Control-LV-HCT116 cells and in shRNA-CBFß-LV cells compared to the shRNA-Control-LV cells analyzed by RNA-seq