AI Article Synopsis
- Deficiency in DNA repair pathways, especially the base excision repair (BER) pathway, plays a key role in the development of colorectal cancer (CRC), with the function of NEIL1 in this context being particularly significant.
- NEIL1 is found to be highly expressed in CRC tissues and is linked to worse clinical outcomes; its knockout in mice reduces tumor growth and enhances immune response through increased CD8 T cell infiltration.
- The study indicates that NEIL1 promotes the expression of immunosuppressive factors by forming a complex with SATB2 and c-Myc, and suggests that targeting both NEIL1 and NF-κB could be an effective new approach for treating CRC.
Article 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 Apc 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2023.113654 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!