Function and mechanism of MCM8 in the development and progression of colorectal cancer
Abstract Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04084-9 |
| _version_ | 1797556843603558400 |
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| author | Shaojun Yu Weixing Dai Senlin Zhao Yongzhi Yang Ye Xu Jianwei Wang Qun Deng Jinghu He Debing Shi |
| author_facet | Shaojun Yu Weixing Dai Senlin Zhao Yongzhi Yang Ye Xu Jianwei Wang Qun Deng Jinghu He Debing Shi |
| author_sort | Shaojun Yu |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8 was found to be upregulated in CRC tissues and significantly associated with tumor grade and patients’ survival. Knocking down MCM8 expression in CRC cells could restrain cell growth and cell motility while promoting cell apoptosis in vitro, as well as inhibit tumor growth in xenograft mice model. Based on the RNA screening performing on CRC cells with or without MCM8 knockdown and the following IPA analysis, CHSY1 was identified as a potential target of MCM8 in CRC, whose expression was also found to be higher in tumor tissues than in normal tissues. Moreover, it was demonstrated that MCM8 may regulate the expression of CHSY1 through affecting its NEDD4-mediated ubiquitination, both of which synergistically execute tumor promotion effects on CRC. In conclusion, the outcomes of our study showed the first evidence that MCM8 act as a tumor promotor in CRC, and may be a promising therapeutic target of CRC treatment. |
| first_indexed | 2024-03-10T17:08:41Z |
| format | Article |
| id | doaj.art-4d2f9f14bc4b457ea8dac03eb7a6df44 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-10T17:08:41Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-4d2f9f14bc4b457ea8dac03eb7a6df442023-11-20T10:44:11ZengBMCJournal of Translational Medicine1479-58762023-09-0121111410.1186/s12967-023-04084-9Function and mechanism of MCM8 in the development and progression of colorectal cancerShaojun Yu0Weixing Dai1Senlin Zhao2Yongzhi Yang3Ye Xu4Jianwei Wang5Qun Deng6Jinghu He7Debing Shi8Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Ministry of Education, Zhejiang University School of MedicineDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Ministry of Education, Zhejiang University School of MedicineDepartment of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Ministry of Education, Zhejiang University School of MedicineDepartment of General Surgery, Changhai Hospital Affiliated to Navy Medical UniversityDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterAbstract Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8 was found to be upregulated in CRC tissues and significantly associated with tumor grade and patients’ survival. Knocking down MCM8 expression in CRC cells could restrain cell growth and cell motility while promoting cell apoptosis in vitro, as well as inhibit tumor growth in xenograft mice model. Based on the RNA screening performing on CRC cells with or without MCM8 knockdown and the following IPA analysis, CHSY1 was identified as a potential target of MCM8 in CRC, whose expression was also found to be higher in tumor tissues than in normal tissues. Moreover, it was demonstrated that MCM8 may regulate the expression of CHSY1 through affecting its NEDD4-mediated ubiquitination, both of which synergistically execute tumor promotion effects on CRC. In conclusion, the outcomes of our study showed the first evidence that MCM8 act as a tumor promotor in CRC, and may be a promising therapeutic target of CRC treatment.https://doi.org/10.1186/s12967-023-04084-9Colorectal cancerMCM8CHSY1Tumor promotorMolecular mechanism |
| spellingShingle | Shaojun Yu Weixing Dai Senlin Zhao Yongzhi Yang Ye Xu Jianwei Wang Qun Deng Jinghu He Debing Shi Function and mechanism of MCM8 in the development and progression of colorectal cancer Journal of Translational Medicine Colorectal cancer MCM8 CHSY1 Tumor promotor Molecular mechanism |
| title | Function and mechanism of MCM8 in the development and progression of colorectal cancer |
| title_full | Function and mechanism of MCM8 in the development and progression of colorectal cancer |
| title_fullStr | Function and mechanism of MCM8 in the development and progression of colorectal cancer |
| title_full_unstemmed | Function and mechanism of MCM8 in the development and progression of colorectal cancer |
| title_short | Function and mechanism of MCM8 in the development and progression of colorectal cancer |
| title_sort | function and mechanism of mcm8 in the development and progression of colorectal cancer |
| topic | Colorectal cancer MCM8 CHSY1 Tumor promotor Molecular mechanism |
| url | https://doi.org/10.1186/s12967-023-04084-9 |
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