PMID- 32047362 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220412 IS - 1475-2867 (Print) IS - 1475-2867 (Electronic) IS - 1475-2867 (Linking) VI - 20 DP - 2020 TI - The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein. PG - 44 LID - 10.1186/s12935-020-1127-0 [doi] LID - 44 AB - 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. CI - (c) The Author(s) 2020. FAU - Mao, Cheng-Gang AU - Mao CG AD - 1Department of Otolaryngology-Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, 1 Ren-Min Road, Jingzhou, 434020 People's Republic of China. GRID: grid.410654.2 FAU - Zhou, Xiao-Chun AU - Zhou XC AD - 1Department of Otolaryngology-Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, 1 Ren-Min Road, Jingzhou, 434020 People's Republic of China. GRID: grid.410654.2 FAU - Jiang, Yi-Dao AU - Jiang YD AUID- ORCID: 0000-0001-5261-9487 AD - 1Department of Otolaryngology-Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, 1 Ren-Min Road, Jingzhou, 434020 People's Republic of China. GRID: grid.410654.2 FAU - Wan, Li-Jia AU - Wan LJ AD - 1Department of Otolaryngology-Head and Neck Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, 1 Ren-Min Road, Jingzhou, 434020 People's Republic of China. GRID: grid.410654.2 FAU - Tao, Ze-Zhang AU - Tao ZZ AD - 2Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060 People's Republic of China. ISNI: 0000 0004 1758 2270. GRID: grid.412632.0 FAU - Guo, Jun AU - Guo J AD - 3Department of Oncology, Affiliated Dongfeng Hospital, Hubei University of Medicine, No. 10, Daling Road, Shiyan, 442008 Hubei People's Republic of China. ISNI: 0000 0004 1799 2448. GRID: grid.443573.2 LA - eng PT - Journal Article DEP - 20200207 PL - England TA - Cancer Cell Int JT - Cancer cell international JID - 101139795 PMC - PMC7006165 OTO - NOTNLM OT - Evi5 OT - Laryngeal squamous cell carcinoma OT - Ubiquitination OT - c-Myc COIS- Competing interestsThe authors declare that they have no competing interests. EDAT- 2020/02/13 06:00 MHDA- 2020/02/13 06:01 PMCR- 2020/02/07 CRDT- 2020/02/13 06:00 PHST- 2019/11/28 00:00 [received] PHST- 2020/01/29 00:00 [accepted] PHST- 2020/02/13 06:00 [entrez] PHST- 2020/02/13 06:00 [pubmed] PHST- 2020/02/13 06:01 [medline] PHST- 2020/02/07 00:00 [pmc-release] AID - 1127 [pii] AID - 10.1186/s12935-020-1127-0 [doi] PST - epublish SO - Cancer Cell Int. 2020 Feb 7;20:44. doi: 10.1186/s12935-020-1127-0. eCollection 2020.