2. Academic Validation
  3. NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1

NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1

  • Cell Rep. 2024 Jan 3;43(1):113654. doi: 10.1016/j.celrep.2023.113654.
Jing-Hua Cao 1,  Chen-Hui Cao 2,  Jin-Long Lin 1,  Si-Yu Li 1,  Long-Jun He 3,  Kai Han 4,  Jie-Wei Chen 5,  Si Li 1,  Xin Wang 6,  Dan Xie 7,  Feng-Wei Wang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 2 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, P.R. China.
  • 3 Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 4 Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 5 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 6 Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 7 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: xiedan@sysucc.org.cn.
  • 8 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: wangfengw@sysucc.org.cn.
PMID: 38175757 DOI: 10.1016/j.celrep.2023.113654
Abstract

Deficiency of DNA repair pathways drives the development of colorectal Cancer. However, the role of the base excision repair (BER) pathway in colorectal Cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal Cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in APCMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.

Keywords

COL17A1; CP: Cancer; DNA repair; NEIL1; colorectal cancer.

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