NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1
Summary: 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)...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723016650 |
| _version_ | 1797366571710021632 |
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| author | Jing-Hua Cao Chen-Hui Cao Jin-Long Lin Si-Yu Li Long-Jun He Kai Han Jie-Wei Chen Si Li Xin Wang Dan Xie Feng-Wei Wang |
| author_facet | Jing-Hua Cao Chen-Hui Cao Jin-Long Lin Si-Yu Li Long-Jun He Kai Han Jie-Wei Chen Si Li Xin Wang Dan Xie Feng-Wei Wang |
| author_sort | Jing-Hua Cao |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-08T17:06:38Z |
| format | Article |
| id | doaj.art-2c18c18dc0da421798f8dd29eaf7fe92 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T17:06:38Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2c18c18dc0da421798f8dd29eaf7fe922024-01-04T04:39:22ZengElsevierCell Reports2211-12472024-01-01431113654NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1Jing-Hua Cao0Chen-Hui Cao1Jin-Long Lin2Si-Yu Li3Long-Jun He4Kai Han5Jie-Wei Chen6Si Li7Xin Wang8Dan Xie9Feng-Wei Wang10State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaState 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. ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaDepartment of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center of Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaDepartment of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. ChinaState 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; Corresponding authorState 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723016650CP: Cancer |
| spellingShingle | Jing-Hua Cao Chen-Hui Cao Jin-Long Lin Si-Yu Li Long-Jun He Kai Han Jie-Wei Chen Si Li Xin Wang Dan Xie Feng-Wei Wang NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 Cell Reports CP: Cancer |
| title | NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 |
| title_full | NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 |
| title_fullStr | NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 |
| title_full_unstemmed | NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 |
| title_short | NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1 |
| title_sort | neil1 drives the initiation of colorectal cancer through transcriptional regulation of col17a1 |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723016650 |
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