UBE2T Promotes Proliferation of Oral Squamous Cell Carcinoma by Activating AKT Signaling Pathway

doi:10.13701/j.cnki.kqyxyj.2026.10.009

Abstract

Abstract: Objective: To investigate the expression of ubiquitin-conjugating enzyme E2T (UBE2T) in oral squamous cell carcinoma tissues and cells, as well as its effects on the biological behaviors of oral squamous cell carcinoma (OSCC) cells including proliferation, invasion, and migration, along with the related mechanisms. Methods: The TIMER database and GEPIA database were used to analyze the expression level of UBE2T-mRNA in head and neck squamous cell carcinoma tissues. Immunohistochemistry was employed to validate UBE2T expression in OSCC tissues. Statistical methods were used to assess the relationship between UBE2T expression and the clinical pathological characteristics and prognosis of OSCC patients. Western blotting and real-time quantitative PCR were utilized to validate UBE2T expression levels in OSCC cell lines. After transfection with UBE2T interfering mRNA, the effect of UBE2T on the biological behavior of the OSCC cell line CAL-27 through in vitro cell experiments was validated and the expression of the protein kinase B (AKT) signaling pathway after interference was detected. Results: Compared with adjacent and normal tissues, UBE2T expression was significantly elevated in OSCC (P<0.05). The overall survival time in the high UBE2T expression group was markedly shorter than that in the low expression group (P<0.05). The differentiation degree of OSCC showed a negative correlation with UBE2T expression (P<0.05). Compared with the si-NC group, CAL-27 cells transfected with si-UBE2T exhibited significantly lower proliferation, migration, and invasion capacities (P<0.05). Compared with the si-NC group, the si-UBE2T group showed significantly reduced levels of phosphorylated protein kinase B protein (P<0.05). Conclusion: UBE2T is highly expressed in OSCC tissues and associated with significantly shorter patient survival. Silencing UBE2T expression reduced the proliferation, invasion, and migration abilities of OSCC cells, potentially through regulating the phosphorylated AKT signaling pathway to modulate OSCC cell proliferation.

Key words: oral squamous cell carcinoma, ubiquitin-conjugating enzyme E2T, protein kinase B, cell migration, cell proliferation

YANG Sen, WANG Huiyu, ZHANG Jiajia, FANG Taoli, XU Jiang. UBE2T Promotes Proliferation of Oral Squamous Cell Carcinoma by Activating AKT Signaling Pathway[J]. Journal of Oral Science Research, 2026, 42(10): 877-883.

References

[1] Singh P, Rai A, Verma AK, et al. Survival-based biomarker module identification associated with Oral squamous cell carcinoma (OSCC)[J]. Biology (Basel), 2021, 10(8):760.
[2] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[3] Struckmeier AK, Buchbender M, Lutz R, et al. Improved recurrence rates and progression-free survival in primarily surgically treated oral squamous cell carcinoma-results from a German tertiary medical center[J]. Clin Oral Investig, 2024, 28(5): 262.
[4] Ma N, Li Z, Yan J, et al. Diverse roles of UBE2T in cancer (Review)[J]. Oncol Rep, 2023, 49(4):69.
[5] Cornwell MJ, Thomson GJ, Coates J, et al. Small-molecule inhibition of UBE2T/FANCL-mediated ubiquitylation in the fanconi anemia pathway[J]. ACS Chem Biol, 2019, 14(10): 2148-2154.
[6] Wu M, Li X, Huang W, et al. Ubiquitin-conjugating enzyme E2T(UBE2T) promotes colorectal cancer progression by facilitating ubiquitination and degradation of p53[J]. Clin Res Hepatol Gastroenterol, 2021, 45(2): 101493.
[7] Mumtaz M, Bijnsdorp IV, Bottger F, et al. Secreted protein markers in oral squamous cell carcinoma (OSCC)[J]. Clin Proteomics, 2022, 19(1): 4.
[8] Lin X, Wu W, Ying Y, et al. MicroRNA-31: a pivotal oncogenic factor in oral squamous cell carcinoma[J]. Cell Death Discov, 2022, 8(1): 140.
[9] Zhou F, Sun Y, Chen X, et al. UBE2T-mediated HP1alpha ubiquitination enhances nucleolar function and promotes the progression of IDH1/TP53-mutant glioma[J]. Clin Cancer Res, 2025, 31(18): 3970-3983.
[10] Gao C, Liu YJ, Yu J, et al. Unraveling the role of ubiquitin-conjugating enzyme UBE2T in tumorigenesis: a comprehensive review[J]. Cells, 2024, 14(1):15.
[11] Yu Z, Jiang X, Qin L, et al. A novel UBE2T inhibitor suppresses wnt/beta-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination[J]. Oncogene, 2021, 40(5): 1027-1042.
[12] Jiang X, Ma Y, Wang T, et al. Targeting UBE2T potentiates gemcitabine efficacy in pancreatic cancer by regulating pyrimidine metabolism and replication Stress[J]. Gastroenterology, 2023, 164(7): 1232-1247.
[13] Shi LL, Chen Y, Xie MX, et al. UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy[J]. J Immunother Cancer, 2025, 13(2):e010782.
[14] Wu Y, Wang Y, Liu H, et al. Mechanism of apoptosis in oral squamous cell carcinoma promoted by cardamonin through PI3K/AKT signaling pathway[J]. Sci Rep, 2024, 14(1): 20802.
[15] Hu W, Xiao L, Cao C, et al. UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3β/β-catenin pathway[J]. Oncotarget, 2016, 7(12): 15161-15172.
[16] Cui P, Li H, Wang C, et al. UBE2T regulates epithelial-mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer[J]. J Ovarian Res, 2022, 15(1): 103.
[17] Song M, Bode AM, Dong Z, et al. AKT as a therapeutic target for cancer[J]. Cancer Res, 2019, 79(6): 1019-1031.
[18] Hassan D, Menges CW, Testa JR, et al. AKT kinases as therapeutic targets[J]. J Exp Clin Cancer Res, 2024, 43(1): 313.