UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion by promoting epithelial-mesenchymal transition via inhibiting autophagy in an AKT/mTOR dependent manner in ovarian cancer

References

• Nash Z, Menon U. Ovarian cancer screening: current status and future directions. Best Pract Res Clin Obstet Gynaecol. 2020;65:32–45.
   PubMed Web of Science ®Google Scholar
• Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med. 2019;8:7018–7031.
   PubMed Web of Science ®Google Scholar
• Hosseini SM, Okoye I, Chaleshtari MG, et al. E2 ubiquitin-conjugating enzymes in cancer: implications for immunotherapeutic interventions. Clin Chim Acta. 2019;498:126–134.
   PubMed Web of Science ®Google Scholar
• Alpi AF, Chaugule V, Walden H. Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3. Biochem J. 2016;473:3401–3419.
   PubMed Web of Science ®Google Scholar
• Luo C, Yao Y, Yu Z, et al. UBE2T knockdown inhibits gastric cancer progression. Oncotarget. 2017;8:32639–32654.
   PubMedGoogle Scholar
• Yu H, Xiang P, Pan Q, et al. Ubiquitin-conjugating enzyme E2T is an independent prognostic factor and promotes gastric cancer progression. Tumour Biol. 2016;37:11723–11732.
   PubMedGoogle Scholar
• Liu LP, Yang M, Peng QZ, et al. UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53. Biochem Biophys Res Commun. 2017;493:20–27.
   PubMed Web of Science ®Google Scholar
• Perez-Pena J, Corrales-Sanchez V, Amir E, et al. Ubiquitin-conjugating enzyme E2T (UBE2T) and denticleless protein homolog (DTL) are linked to poor outcome in breast and lung cancers. Sci Rep. 2017;7:17530.
   PubMed Web of Science ®Google Scholar
• Wu ZH, Zhang YJ, Sun HY. High ubiquitin conjugating enzyme E2 T mRNA expression and its prognostic significance in lung adenocarcinoma: a study based on the TCGA database. Medicine (Baltimore). 2020;99:e18543.
   PubMed Web of Science ®Google Scholar
• Hu W, Xiao L, Cao C, et al. UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3beta/beta-catenin pathway. Oncotarget. 2016;7:15161–15172.
   PubMedGoogle Scholar
• Shen L, Zhao K, Li H, et al. Downregulation of UBE2T can enhance the radiosensitivity of osteosarcoma in vitro and in vivo. Epigenomics. 2019;11:1283–1305.
   PubMed Web of Science ®Google Scholar
• Wen M, Kwon Y, Wang Y, et al. Elevated expression of UBE2T exhibits oncogenic properties in human prostate cancer. Oncotarget. 2015;6:25226–25239.
   PubMedGoogle Scholar
• Hao P, Kang B, Li Y, et al. UBE2T promotes proliferation and regulates PI3K/Akt signaling in renal cell carcinoma. Mol Med Rep. 2019;20:1212–1220.
   PubMed Web of Science ®Google Scholar
• Alagpulinsa DA, Kumar S, Talluri S, et al. Amplification and overexpression of E2 ubiquitin conjugase UBE2T promotes homologous recombination in multiple myeloma. Blood Adv. 2019;3:3968–3972.
   PubMed Web of Science ®Google Scholar
• Liu J, Liu X. UBE2T silencing inhibited non-small cell lung cancer cell proliferation and invasion by suppressing the wnt/beta-catenin signaling pathway. Int J Clin Exp Pathol. 2017;10:9482–9488.
   PubMed Web of Science ®Google Scholar
• Yin H, Wang X, Zhang X, et al. UBE2T promotes radiation resistance in non-small cell lung cancer via inducing epithelial-mesenchymal transition and the ubiquitination-mediated FOXO1 degradation. Cancer Lett. 2020;494:121–131.
   PubMed Web of Science ®Google Scholar
• Huang P, Guo Y, Zhao Z, et al. UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT. Aging (Albany NY). 2020;12:10275–10289.
   PubMedGoogle Scholar
• Ueki T, Park JH, Nishidate T, et al. Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells. Cancer Res. 2009;69:8752–8760.
   PubMed Web of Science ®Google Scholar
• Zou R, Xu H, Li F, et al. Increased expression of UBE2T predicting poor survival of epithelial ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples, and the GEO database. DNA Cell Biol. 2021;40:36–60.
   PubMed Web of Science ®Google Scholar
• Huang T, Song X, Yang Y, et al. Autophagy and hallmarks of cancer. Crit Rev Oncog. 2018;23:247–267.
   PubMedGoogle Scholar
• Huang W, Zeng C, Liu J, et al. Sodium butyrate induces autophagic apoptosis of nasopharyngeal carcinoma cells by inhibiting AKT/mTOR signaling. Biochem Biophys Res Commun. 2019;514:64–70.
   PubMed Web of Science ®Google Scholar
• Liu J, Huang W, Ren C, et al. Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-kappaB and PI3K/Akt3 signaling pathways. Sci Rep. 2015;5:11614.
   PubMed Web of Science ®Google Scholar
• Rhodes DR, Yu J, Shanker K, et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004;6:1–6.
   PubMed Web of Science ®Google Scholar
• Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–W102.
   PubMed Web of Science ®Google Scholar
• Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19:649–658.
   PubMed Web of Science ®Google Scholar
• Nagy A, Lanczky A, Menyhart O, et al. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8:9227.
   PubMed Web of Science ®Google Scholar
• Huang W, Liu J, Hu S, et al. miR-181a upregulation promotes radioresistance of nasopharyngeal carcinoma by targeting RKIP. Onco Targets Ther. 2019;12:10873–10884.
   PubMed Web of Science ®Google Scholar
• Zhan L, Zhang Y, Wang W, et al. Autophagy as an emerging therapy target for ovarian carcinoma. Oncotarget. 2016;7:83476–83487.
   PubMedGoogle Scholar
• Zhang W, Zhang Y, Yang Z, et al. High expression of UBE2T predicts poor prognosis and survival in multiple myeloma. Cancer Gene Ther. 2019;26:347–355.
   PubMed Web of Science ®Google Scholar
• Wang Y, Leng H, Chen H, et al. Knockdown of UBE2T inhibits osteosarcoma cell proliferation, migration, and invasion by suppressing the PI3K/Akt signaling pathway. Oncol Res. 2016;24:361–369.
   PubMed Web of Science ®Google Scholar
• Gong YQ, Peng D, Ning XH, et al. UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells. Oncol Lett. 2016;12:4485–4492.
   PubMed Web of Science ®Google Scholar
• Guo J, Wang M, Wang J, Wu C. (2019). Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis. World J Gastroenterol, 25(43), 6386–6403. https://doi.org/10.3748/wjg.v25.i43.6386
   PubMed Web of Science ®Google Scholar
• Liu L, Yang M, Peng Q, Li M, Zhang Y, Guo Y, Chen Y, Bao S. (2017). UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53. Biochem Biophys Res Commun, 493(1), 20–27. https://doi.org/10.1016/j.bbrc.2017.09.091
   PubMed Web of Science ®Google Scholar
• Ikeda F. Ubiquitin conjugating enzymes in the regulation of the autophagy-dependent degradation pathway. Matrix Biol. 2021;100–101:23–29.
   PubMed Web of Science ®Google Scholar
• Falvey CM, O’Donovan TR, El-Mashed S, et al. UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells. Oncotarget. 2017;8:23479–23491.
   PubMedGoogle Scholar
• Geisler S, Vollmer S, Golombek S, et al. The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. J Cell Sci. 2014;127:3280–3293.
   PubMed Web of Science ®Google Scholar
• Kma L, Baruah TJ. The interplay of ROS and the PI3K/Akt pathway in autophagy regulation. Biotechnol Appl Biochem. 2021. DOI:https://doi.org/10.1002/bab.2104
   Google Scholar
• Grassi G, Di Caprio G, Santangelo L, et al. Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation. Cell Death Dis. 2015;6:e1880.
   PubMed Web of Science ®Google Scholar
• Catalano M, D’Alessandro G, Lepore F, et al. Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells. Mol Oncol. 2015;9:1612–1625.
   PubMed Web of Science ®Google Scholar
• Zada S, Hwang JS, Ahmed M, et al. Control of the epithelial-to-mesenchymal transition and cancer metastasis by autophagy-dependent SNAI1 degradation. Cells. 2019;8:129.
   Web of Science ®Google Scholar