UBE2T regulates epithelial–mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer

Autor: Ping Cui, Hao Li, Can Wang, Yuan Liu, Mengjun Zhang, Yue Yin, Zhenxing Sun, Yiru Wang, Xiuwei Chen
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Ovarian Research, Vol 15, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1757-2215
DOI: 10.1186/s13048-022-01034-9
Popis: Abstract Background Ubiquitin-binding enzyme E2T (UBE2T), a member of the E2 family of the ubiquitin–proteasome pathway, is associated with tumorigenesis of varioustumours; however, its role and mechanism in ovarian cancer remain unclear. Results Our study revealed that UBE2T is highly expressed in ovarian cancer; this high expression was closely related to poor prognosis. Immunohistochemistry was used to validate the high expression of UBE2T in ovarian cancer. This is the first study to demonstrate that UBE2T expression is higher in ovarian cancer with BRCA mutation. Moreover, we demonstrated that UBE2T gene silencing significantly inhibited ovarian cancer cell proliferation and invasion. The epithelial–mesenchymal transition (EMT) of ovarian cancer cells and phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) pathway were significantly inhibited. Adding the mechanistic target of rapamycin activator MHY1485 activated the PI3K-AKT pathway and significantly restored the proliferative and invasive ability of ovarian cancer cells. Furthermore, a tumorigenesis experiment in nude mice revealed that tumour growth on mice body surface and tumour tissue EMT were significantly inhibited after UBE2T gene silencing. Conclusions This study demonstrated that UBE2T regulates EMT via the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer. Moreover, UBE2T may interact with BRCA to affect ovarian cancer occurrence and development. Hence, UBE2T may be a valuable novel biomarker for the early diagnosis and prognosis and treatment of ovarian cancer. Further, UBE2T inhibition may be effective for treating ovarian cancer.
Databáze: Directory of Open Access Journals
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