STAT3-Mediated Promoter-Enhancer Interaction Up-Regulates Inhibitor of DNA Binding 1 () to Promote Colon Cancer Progression.

Background: High expression of inhibitor of DNA binding 1 () correlates with poor prognosis in colorectal cancer (CRC). Aberrant enhancer activation in regulating transcription is limited.

Methods: Immunohistochemistry (IHC), quantitative RT-PCR (RT-qPCR) and Western blotting (WB) were used to determine the expression of . CRISPR-Cas9 was used to generate or enhancer E1 knockout cell lines. Dual-luciferase reporter assay, chromosome conformation capture assay and ChIP-qPCR were used to determine the active enhancers of . Cell Counting Kit 8, colony-forming, transwell assays and tumorigenicity in nude mice were used to investigate the biological functions of and enhancer E1.

Results: Human CRC tissues and cell lines expressed a higher level of than normal controls. promoted CRC cell proliferation and colony formation. Enhancer E1 actively regulated promoter activity. Signal transducer and activator of transcription 3 (STAT3) bound to promoter and enhancer E1 to regulate their activity. The inhibitor of STAT3 Stattic attenuated promoter and enhancer E1 activity and the expression of . Enhancer E1 knockout down-regulated expression level and cell proliferation in vitro and in vivo.

Conclusions: Enhancer E1 is positively regulated by STAT3 and contributes to the regulation of to promote CRC cell progression and might be a potential target for anti-CRC drug studies.