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.
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.
Cell Rep. 2024 Jan 23;43(1):113654. doi: 10.1016/j.celrep.2023.113654. Epub 2024 Jan 3.
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.
DNA 修复途径的缺陷会导致结直肠癌的发生。然而，碱基切除修复（BER）途径在结直肠癌发生中的作用尚不清楚。本研究表明，Nei 样 DNA 糖苷酶 1（NEIL1）在结直肠癌（CRC）组织中高表达，并与较差的临床结局相关。在小鼠中敲除 neil1 可显著抑制肿瘤发生，并增强肠道肿瘤中 CD8 T 细胞的浸润。此外，NEIL1 可直接与 SATB2/c-Myc 形成复合物，增强 COL17A1 的转录，进而促进 CRC 细胞中免疫抑制细胞因子的产生。NEIL1 肽可抑制 Apc 小鼠的肠道肿瘤发生，而靶向 NEIL1 与核因子 κB（NF-κB）抑制剂联合使用可显示出对肿瘤生长的协同抑制作用。这些结果表明，联合靶向 NEIL1 和 NF-κB 可能代表一种有前途的 CRC 治疗策略。
