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UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis

BACKGROUND: Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV....

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Autores principales: Zhang, Mengjun, Liu, Yuan, Yin, Yue, Sun, Zhenxing, Wang, Yan, Zhang, Zexue, Li, Fei, Chen, Xiuwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166599/
https://www.ncbi.nlm.nih.gov/pubmed/35658829
http://dx.doi.org/10.1186/s10020-022-00489-2
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author Zhang, Mengjun
Liu, Yuan
Yin, Yue
Sun, Zhenxing
Wang, Yan
Zhang, Zexue
Li, Fei
Chen, Xiuwei
author_facet Zhang, Mengjun
Liu, Yuan
Yin, Yue
Sun, Zhenxing
Wang, Yan
Zhang, Zexue
Li, Fei
Chen, Xiuwei
author_sort Zhang, Mengjun
collection PubMed
description BACKGROUND: Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV. Ubiquitin-conjugating enzyme E2S (UBE2S), a potential oncogene, regulates the malignant progression of various tumors; however, its role in OV is still unclear. METHODS: The expression and prognostic significance of UBE2S at the pan-cancer level were investigated through high-throughput gene expression analysis and clinical prognostic data from TCGA, GEPIA, and GEO databases. 181 patients with OV were included in this study. Cell culture and cell transfection were performed on OV cell lines (SKOV3 and A2780) and a normal ovarian cell line (IOSE80). The expression level and prognostic significance of UBE2S in OV were verified by western blot, immunohistochemistry, and Kaplan–Meier survival analysis. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, Transwell, clonogenic, and flow cytometry assays, the effect and detailed mechanism of UBE2S knockdown on the malignant biological behavior of OV cells were explored. RESULTS: UBE2S exhibited abnormally high expression at the pan-cancer level. The results of RT-qPCR and Western blotting indicated that UBE2S was significantly overexpressed in ovarian cancer cell lines compared with normal cell lines (P < 0.05). Kaplan–Meier survival analysis and Immunohistochemistry indicated that overexpression of UBE2S was related to poor prognosis of OV (HR > 1, P < 0.05). Results of in vitro experiments indicated that UBE2S gene knockdown might inhibit the proliferation, invasion, and prognosis of OV cells by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby blocking the cell cycle and promoting apoptosis (P < 0.05). CONCLUSION: UBE2S is a potential oncogene strongly associated with a poor prognosis of OV patients. Knockdown of UBE2S could block the cell cycle and promote apoptosis by inhibiting the PI3K/AKT/mTOR pathway and ultimately inhibit the proliferation, migration and prognosis of ovarian cancer, which suggested that UBE2S might be used for molecular therapy and prognostic evaluation of ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00489-2.
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spelling pubmed-91665992022-06-05 UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis Zhang, Mengjun Liu, Yuan Yin, Yue Sun, Zhenxing Wang, Yan Zhang, Zexue Li, Fei Chen, Xiuwei Mol Med Research Article BACKGROUND: Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV. Ubiquitin-conjugating enzyme E2S (UBE2S), a potential oncogene, regulates the malignant progression of various tumors; however, its role in OV is still unclear. METHODS: The expression and prognostic significance of UBE2S at the pan-cancer level were investigated through high-throughput gene expression analysis and clinical prognostic data from TCGA, GEPIA, and GEO databases. 181 patients with OV were included in this study. Cell culture and cell transfection were performed on OV cell lines (SKOV3 and A2780) and a normal ovarian cell line (IOSE80). The expression level and prognostic significance of UBE2S in OV were verified by western blot, immunohistochemistry, and Kaplan–Meier survival analysis. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, Transwell, clonogenic, and flow cytometry assays, the effect and detailed mechanism of UBE2S knockdown on the malignant biological behavior of OV cells were explored. RESULTS: UBE2S exhibited abnormally high expression at the pan-cancer level. The results of RT-qPCR and Western blotting indicated that UBE2S was significantly overexpressed in ovarian cancer cell lines compared with normal cell lines (P < 0.05). Kaplan–Meier survival analysis and Immunohistochemistry indicated that overexpression of UBE2S was related to poor prognosis of OV (HR > 1, P < 0.05). Results of in vitro experiments indicated that UBE2S gene knockdown might inhibit the proliferation, invasion, and prognosis of OV cells by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby blocking the cell cycle and promoting apoptosis (P < 0.05). CONCLUSION: UBE2S is a potential oncogene strongly associated with a poor prognosis of OV patients. Knockdown of UBE2S could block the cell cycle and promote apoptosis by inhibiting the PI3K/AKT/mTOR pathway and ultimately inhibit the proliferation, migration and prognosis of ovarian cancer, which suggested that UBE2S might be used for molecular therapy and prognostic evaluation of ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00489-2. BioMed Central 2022-06-03 /pmc/articles/PMC9166599/ /pubmed/35658829 http://dx.doi.org/10.1186/s10020-022-00489-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Zhang, Mengjun
Liu, Yuan
Yin, Yue
Sun, Zhenxing
Wang, Yan
Zhang, Zexue
Li, Fei
Chen, Xiuwei
UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title_full UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title_fullStr UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title_full_unstemmed UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title_short UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
title_sort ube2s promotes the development of ovarian cancer by promoting pi3k/akt/mtor signaling pathway to regulate cell cycle and apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166599/
https://www.ncbi.nlm.nih.gov/pubmed/35658829
http://dx.doi.org/10.1186/s10020-022-00489-2
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