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UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma
PURPOSE: The purpose of this paper was to investigate the expression and function of Ubiquitin-conjugating enzyme 2T (UBE2T), a human E2 ubiquitin-conjugating enzyme, in human retinoblastoma. METHODS: The expression of UBE2T in normal retina and retinoblastoma was analyzed using the Gene Expression...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404369/ https://www.ncbi.nlm.nih.gov/pubmed/35980647 http://dx.doi.org/10.1167/iovs.63.9.20 |
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author | Xu, Nuo Cui, Yi Shi, Hong Guo, Guodong Sun, Fengyuan Jian, Tianming Rao, Huiying |
author_facet | Xu, Nuo Cui, Yi Shi, Hong Guo, Guodong Sun, Fengyuan Jian, Tianming Rao, Huiying |
author_sort | Xu, Nuo |
collection | PubMed |
description | PURPOSE: The purpose of this paper was to investigate the expression and function of Ubiquitin-conjugating enzyme 2T (UBE2T), a human E2 ubiquitin-conjugating enzyme, in human retinoblastoma. METHODS: The expression of UBE2T in normal retina and retinoblastoma was analyzed using the Gene Expression Omnibus (GEO) databases, and its expression was immunohistochemically evaluated in 29 retinoblastoma sections and 5 normal retinas. Then CCK-8, flow cytometry, RNA-sequencing analysis, and in vivo assays were performed to explore the exact role of UBE2T in retinoblastoma. RESULTS: We found that retinoblastoma showed higher UBE2T expression than normal retina in GEO datasets and tissues. The immunoreactive score of UBE2T ≥4 was associated with group E in IIRC, T2-T4b in pTNM staging, poorly differentiated retinoblastoma, and high-risk histopathological factors. Knockdown of UBE2T reduced the cell viability, increased the apoptosis cells and G0/G1 cells, and inhibited subcutaneous tumor growth in vivo. Mechanistic studies showed that UBE2T knockdown induced down-regulation of phosphorylation of STAT3 and its downstream genes in vitro and in vivo. Rescue assays confirmed that STAT3 signaling pathway was involved in the effect of reduced cell viability, elevated apoptosis cells, and G0/G1 cells mediated by UBE2T knockdown. CONCLUSIONS: Our data indicate that UBE2T significantly participates in the proliferation of retinoblastoma via the STAT3 signaling pathway, suggesting the potential of UBE2T as a therapeutic target for retinoblastoma treatment. |
format | Online Article Text |
id | pubmed-9404369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-94043692022-08-26 UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma Xu, Nuo Cui, Yi Shi, Hong Guo, Guodong Sun, Fengyuan Jian, Tianming Rao, Huiying Invest Ophthalmol Vis Sci Anatomy and Pathology/Oncology PURPOSE: The purpose of this paper was to investigate the expression and function of Ubiquitin-conjugating enzyme 2T (UBE2T), a human E2 ubiquitin-conjugating enzyme, in human retinoblastoma. METHODS: The expression of UBE2T in normal retina and retinoblastoma was analyzed using the Gene Expression Omnibus (GEO) databases, and its expression was immunohistochemically evaluated in 29 retinoblastoma sections and 5 normal retinas. Then CCK-8, flow cytometry, RNA-sequencing analysis, and in vivo assays were performed to explore the exact role of UBE2T in retinoblastoma. RESULTS: We found that retinoblastoma showed higher UBE2T expression than normal retina in GEO datasets and tissues. The immunoreactive score of UBE2T ≥4 was associated with group E in IIRC, T2-T4b in pTNM staging, poorly differentiated retinoblastoma, and high-risk histopathological factors. Knockdown of UBE2T reduced the cell viability, increased the apoptosis cells and G0/G1 cells, and inhibited subcutaneous tumor growth in vivo. Mechanistic studies showed that UBE2T knockdown induced down-regulation of phosphorylation of STAT3 and its downstream genes in vitro and in vivo. Rescue assays confirmed that STAT3 signaling pathway was involved in the effect of reduced cell viability, elevated apoptosis cells, and G0/G1 cells mediated by UBE2T knockdown. CONCLUSIONS: Our data indicate that UBE2T significantly participates in the proliferation of retinoblastoma via the STAT3 signaling pathway, suggesting the potential of UBE2T as a therapeutic target for retinoblastoma treatment. The Association for Research in Vision and Ophthalmology 2022-08-18 /pmc/articles/PMC9404369/ /pubmed/35980647 http://dx.doi.org/10.1167/iovs.63.9.20 Text en Copyright 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Anatomy and Pathology/Oncology Xu, Nuo Cui, Yi Shi, Hong Guo, Guodong Sun, Fengyuan Jian, Tianming Rao, Huiying UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title | UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title_full | UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title_fullStr | UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title_full_unstemmed | UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title_short | UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma |
title_sort | ube2t/stat3 signaling promotes the proliferation and tumorigenesis in retinoblastoma |
topic | Anatomy and Pathology/Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404369/ https://www.ncbi.nlm.nih.gov/pubmed/35980647 http://dx.doi.org/10.1167/iovs.63.9.20 |
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