HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification
Abstract Aerobic glycolysis has been shown to play a key role in tumor cell proliferation and metastasis. However, how it is directly regulated is largely unknown. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 ex...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-11-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01707-4 |
| _version_ | 1797578088935063552 |
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| author | Jiayu Wang Mengxin Zhu Jinghan Zhu Juntao Li Xingchao Zhu Kun Wang Kanger Shen Kexi Yang Xiangyu Ni Xin Liu Guangbo Zhang Qinhua Xi Tongguo Shi Weichang Chen |
| author_facet | Jiayu Wang Mengxin Zhu Jinghan Zhu Juntao Li Xingchao Zhu Kun Wang Kanger Shen Kexi Yang Xiangyu Ni Xin Liu Guangbo Zhang Qinhua Xi Tongguo Shi Weichang Chen |
| author_sort | Jiayu Wang |
| collection | DOAJ |
| description | Abstract Aerobic glycolysis has been shown to play a key role in tumor cell proliferation and metastasis. However, how it is directly regulated is largely unknown. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 expression is associated with poor survival in CRC patients. HES1 knockdown markedly inhibited cell growth and metastasis both in vitro and in vivo. Additionally, silencing of HES1 suppressed aerobic glycolysis of CRC cells. Mechanistic studies revealed that HES1 knockdown decreased the expression of GLUT1, a key gene of aerobic glycolysis, in CRC cells. GLUT1 overexpression abolished the effects of HES1 knockdown on cell aerobic glycolysis, proliferation, migration and invasion. ChIP-PCR and dual-luciferase reporter gene assay showed that HES1 directly bound the promoter of IGF2BP2 and promoted IGF2BP2 expression. Furthermore, our data indicated that IGF2BP2 recognized and bound the m6A site in the GLUT1 mRNA and enhanced its stability. Taken together, our findings suggest that HES1 has a significant promotion effect on CRC aerobic glycolysis and progression by enhancing the stability of m6A-modified GLUT1 mRNA in an IGF2BP2-dependent manner, which may become a viable therapeutic target for the treatment of CRC in humans. The mechanism of HES1 regulating glycolysis in CRC. |
| first_indexed | 2024-03-10T22:18:15Z |
| format | Article |
| id | doaj.art-474eeaf016cf4acbae3fa3766fda4b73 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-10T22:18:15Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-474eeaf016cf4acbae3fa3766fda4b732023-11-19T12:22:37ZengNature Publishing GroupCell Death Discovery2058-77162023-11-019111010.1038/s41420-023-01707-4HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modificationJiayu Wang0Mengxin Zhu1Jinghan Zhu2Juntao Li3Xingchao Zhu4Kun Wang5Kanger Shen6Kexi Yang7Xiangyu Ni8Xin Liu9Guangbo Zhang10Qinhua Xi11Tongguo Shi12Weichang Chen13Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityJiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow UniversityJiangsu Key Laboratory of Clinical Immunology, Soochow UniversityAbstract Aerobic glycolysis has been shown to play a key role in tumor cell proliferation and metastasis. However, how it is directly regulated is largely unknown. Here, we found that HES1 expression was significantly higher in CRC tissues than that in adjacent normal tissues. Moreover, high HES1 expression is associated with poor survival in CRC patients. HES1 knockdown markedly inhibited cell growth and metastasis both in vitro and in vivo. Additionally, silencing of HES1 suppressed aerobic glycolysis of CRC cells. Mechanistic studies revealed that HES1 knockdown decreased the expression of GLUT1, a key gene of aerobic glycolysis, in CRC cells. GLUT1 overexpression abolished the effects of HES1 knockdown on cell aerobic glycolysis, proliferation, migration and invasion. ChIP-PCR and dual-luciferase reporter gene assay showed that HES1 directly bound the promoter of IGF2BP2 and promoted IGF2BP2 expression. Furthermore, our data indicated that IGF2BP2 recognized and bound the m6A site in the GLUT1 mRNA and enhanced its stability. Taken together, our findings suggest that HES1 has a significant promotion effect on CRC aerobic glycolysis and progression by enhancing the stability of m6A-modified GLUT1 mRNA in an IGF2BP2-dependent manner, which may become a viable therapeutic target for the treatment of CRC in humans. The mechanism of HES1 regulating glycolysis in CRC.https://doi.org/10.1038/s41420-023-01707-4 |
| spellingShingle | Jiayu Wang Mengxin Zhu Jinghan Zhu Juntao Li Xingchao Zhu Kun Wang Kanger Shen Kexi Yang Xiangyu Ni Xin Liu Guangbo Zhang Qinhua Xi Tongguo Shi Weichang Chen HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification Cell Death Discovery |
| title | HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification |
| title_full | HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification |
| title_fullStr | HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification |
| title_full_unstemmed | HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification |
| title_short | HES1 promotes aerobic glycolysis and cancer progression of colorectal cancer via IGF2BP2-mediated GLUT1 m6A modification |
| title_sort | hes1 promotes aerobic glycolysis and cancer progression of colorectal cancer via igf2bp2 mediated glut1 m6a modification |
| url | https://doi.org/10.1038/s41420-023-01707-4 |
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