The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein
Abstract Background The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in se...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-1127-0 |
| _version_ | 1818969401097977856 |
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| author | Cheng-Gang Mao Xiao-Chun Zhou Yi-Dao Jiang Li-Jia Wan Ze-Zhang Tao Jun Guo |
| author_facet | Cheng-Gang Mao Xiao-Chun Zhou Yi-Dao Jiang Li-Jia Wan Ze-Zhang Tao Jun Guo |
| author_sort | Cheng-Gang Mao |
| collection | DOAJ |
| description | Abstract Background The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. Methods Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc. Results Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. Conclusion Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy. |
| first_indexed | 2024-12-20T14:20:00Z |
| format | Article |
| id | doaj.art-70e8974d8e984fae9b45e7c99396bdb8 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-20T14:20:00Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-70e8974d8e984fae9b45e7c99396bdb82022-12-21T19:37:56ZengBMCCancer Cell International1475-28672020-02-012011810.1186/s12935-020-1127-0The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc proteinCheng-Gang Mao0Xiao-Chun Zhou1Yi-Dao Jiang2Li-Jia Wan3Ze-Zhang Tao4Jun Guo5Department of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze UniversityDepartment of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze UniversityDepartment of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze UniversityDepartment of Otolaryngology–Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze UniversityDepartment of Otolaryngology–Head and Neck Surgery, Renmin Hospital of Wuhan UniversityDepartment of Oncology, Affiliated Dongfeng Hospital, Hubei University of MedicineAbstract Background The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. Methods Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc. Results Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. Conclusion Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy.https://doi.org/10.1186/s12935-020-1127-0Evi5c-MycLaryngeal squamous cell carcinomaUbiquitination |
| spellingShingle | Cheng-Gang Mao Xiao-Chun Zhou Yi-Dao Jiang Li-Jia Wan Ze-Zhang Tao Jun Guo The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein Cancer Cell International Evi5 c-Myc Laryngeal squamous cell carcinoma Ubiquitination |
| title | The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein |
| title_full | The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein |
| title_fullStr | The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein |
| title_full_unstemmed | The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein |
| title_short | The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein |
| title_sort | evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c myc protein |
| topic | Evi5 c-Myc Laryngeal squamous cell carcinoma Ubiquitination |
| url | https://doi.org/10.1186/s12935-020-1127-0 |
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