NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1
NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1
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DOI：
10.1016/j.celrep.2023.113654
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发表时间：
2024-01-03
期刊：
影响因子：
8.8
通讯作者：
Wang，Feng-Wei
中科院分区：
文献类型：
--
作者：
Cao，Jing-Hua;Cao，Chen-Hui;Wang，Feng-Wei
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仍不清楚。这项研究表明，Nei 样 DNA 糖基化酶 1 (NEIL1) 在结直肠癌 (CRC) 组织中高表达，并与较差的临床结果相关。敲除小鼠中的 outneil1 可显着抑制肿瘤发生并增强肠道肿瘤中 CD8+T 细胞的浸润。此外，NEIL1直接与SATB2/c-Myc形成复合物，增强COL17A1的转录，随后促进CRC细胞中免疫抑制细胞因子的产生。 NEIL1 肽可抑制 ApcMin/+ 小鼠的肠道肿瘤发生，并且当与核因子 κB (NF-κB) 抑制剂联合使用时，靶向 NEIL1 可以对肿瘤生长产生协同抑制作用。这些结果表明，联合靶向 NEIL1 和 NF-κB 可能代表一种有前景的 CRC 治疗策略。
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 outneil1in 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 ofCOL17A1and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis inApcMin/+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.