Downregulation of Sustains the NF-B Pathway by Targeting during the Progression of Colorectal Cancer.

To investigate the role and the underlying mechanism of scaffold attachment factor B () in the progression of colorectal cancer (CRC). SAFB expression was analyzed in the Cancer Outlier Profile Analysis of Oncomine and in 175 paraffin-embedded archived CRC tissues. Gene Ontology analyses were performed to explore the mechanism of in CRC progression. Western blot, RT-PCR, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to detect the regulation of transforming growth factor-β-activated kinase 1 () and NF-κB signaling by The role of SAFB in invasion, metastasis, and angiogenesis was investigated using and assays. The relationship between SAFB and TAK1 was analyzed in CRC tissues. SAFB was downregulated in CRC tissues, and low expression of SAFB was significantly associated with an aggressive phenotype and poorer survival of CRC patients. The downregulation of SAFB activated NF-κB signaling by targeting the promoter. Ectopic expression of SAFB inhibited the development of aggressive features and metastasis of CRC cells both and The overexpression of TAK1 could rescue the aggressive features in SAFB-overexpressed cells. Furthermore, the expression of SAFB in CRC tissues was negatively correlated with the expression of TAK1- and NF-κB-related genes. Our results show that regulated the activity of NF-κB signaling in CRC by targeting This novel mechanism provides a comprehensive understanding of both SAFB and the NF-κB signaling pathway in the progression of CRC and indicates that the SAFB-TAK1-NF-κB axis is a potential target for early therapeutic intervention in CRC progression. .