Discover how the enzyme NEIL1, known for DNA repair, unexpectedly takes center stage in the onset of colorectal cancer by orchestrating the expression of the collagen gene COL17A1, shedding new light on potential therapeutic targets.
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NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1.
Cao et al., Cell Rep 2024
DOI: 10.1016/j.celrep.2023.113654
Summary of Findings:
The study investigates the role of the base excision repair (BER) pathway, specifically focusing on Nei-like DNA glycosylase 1 (NEIL1), in the development of colorectal cancer (CRC). The key findings are:
- NEIL1 Expression: NEIL1 is found to be highly expressed in CRC tissues, and its high expression correlates with worse clinical outcomes.
- NEIL1 Knockout in Mice: Mice lacking neil1 exhibit a significant reduction in intestinal tumorigenesis and an increased infiltration of CD8+ T cells in intestinal tumors.
- Mechanism: NEIL1 interacts with SATB2/c-Myc to upregulate COL17A1 transcription, which in turn promotes the production of immunosuppressive cytokines in CRC cells.
- Therapeutic Potential: A peptide targeting NEIL1 reduces intestinal tumorigenesis in ApcMin/+ mice. Moreover, combining NEIL1 targeting with an NF-κB inhibitor shows a synergistic effect in suppressing tumor growth.
Significance: This research highlights NEIL1 as a potential therapeutic target in CRC. The study’s importance lies in demonstrating the dual role of NEIL1 in CRC progression and immune evasion, providing a novel angle for combination therapy strategies.
Contribution to Literature: The study adds to the understanding of BER pathway involvement in CRC initiation and progression, suggesting a new approach for CRC treatment by targeting NEIL1 alongside NF-κB inhibition.