STAT3-Mediated Promoter-Enhancer Interaction Up-Regulates Inhibitor of DNA Binding 1 ( ID1 ) to Promote Colon Cancer Progression

• Published in: International journal of molecular sciences 2023-06, Vol.24 (12), p.10041
• Main Authors: Lin, Zhike, Liu, Ying, Xu, Tian, Su, Ting, Yang, Yingying, Liang, Runhua, Gu, Songgang, Li, Jie, Song, Xuhong, Liang, Bin, Leng, Zhijun, Li, Yangsihan, Meng, Lele, Luo, Yijing, Chang, Xiaolan, Huang, Dongyang, Xie, Lingzhu
• Format: Article
• Language: English
• Subjects: Animals; Assaying; Binding; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromosomes; Colon cancer; Colonic Neoplasms - genetics; Colonies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Conformation; CRISPR; Deoxyribonucleic acid; Development and progression; DNA; enhancer; Enhancers; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Humans; ID1; Id1 protein; Immunohistochemistry; Inhibitor of Differentiation Protein 1 - genetics; Inhibitor of Differentiation Protein 1 - metabolism; Inhibitors; Luciferase; Mice; Mice, Nude; Prognosis; Proteins; Regulatory Sequences, Nucleic Acid; RNA polymerase; STAT3; Stat3 protein; STAT3 Transcription Factor - metabolism; Transcription activation; Transcription factors; Tumorigenicity; Tumors; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241210041

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