OncoTargets and Therapy (Jun 2020)
UBE2O Promotes Progression and Epithelial–Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
Abstract
Xiyu Chen,1– 3,* Shuiting Zhang,1– 3,* Chao Liu,1– 3 Guo Li,1– 3 Shanhong Lu,1– 3 Yunyun Wang,1– 3 Xin Zhang,1– 3 Donghai Huang,1– 3 Yuanzheng Qiu,1– 4 Yong Liu1– 4 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan 410008, People’s Republic of China; 3Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province, Changsha, Hunan 410008, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, Hunan 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong LiuDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel| Fax +86073184327469Email [email protected]: UBE2O, as a member of the ubiquitin-conjugating enzyme family, is abnormally expressed and exhibits abnormal functions in human malignancies. However, the function of UBE2O in head and neck squamous cell carcinoma (HNSCC) remains unknown. Therefore, our study aims to investigate the role of UBE2O in HNSCC progression and the underlying mechanisms.Methods: The expression of UBE2O in HNSCC patients was investigated with data from the Cancer Genome Atlas (TCGA) and from a separate primary tumor cohort. The function of UBE2O in HNSCC cells was studied by cell viability assay, colony formation assay, wound healing assay, and cell migration and invasion chamber assay. The effect of UBE2O on tumor growth in vivo was determined in a subcutaneous xenograft model of HNSCC.Results: TCGA data showed that UBE2O mRNA expression was dramatically increased in HNSCC tissues and that patients with high expression of UBE2O transcripts had a worse survival prognosis than patients with low expression of UBE2O transcripts. Gain-of-function and loss-of-function analyses revealed that oncogenic UBE2O enhanced the proliferation, migration and invasion of HNSCC cells in vitro. Further, mechanistic analysis revealed that UBE2O induced the epithelial–mesenchymal transition (EMT) phenotype and also potentiated TGF-β 1-induced EMT, and thus leading to an enhanced capacity of migration and invasion in HNSCC. Finally, xenograft models showed that UBE2O knockout obviously inhibited the occurrence of EMT, angiogenesis and tumor growth in HNSCC in vivo.Conclusion: Our study indicates that UBE2O acts as an oncogene to promote the malignant progression and EMT of HNSCC.Keywords: head and neck squamous cell carcinoma, ubiquitin-conjugating enzyme e2o, epithelial–mesenchymal transition, migration, invasion
