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E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma

The E2F3 transcriptional regulatory pathway plays a major part in multiple-cancer progression, but the specific contributions of this pathway to tumor formation and the progression of clear cell renal cell carcinoma (ccRCC) are not fully understood. Clinically, we demonstrated that E2F3 was overexpr...

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Autores principales: Gao, Yu, Li, Hongzhao, Ma, Xin, Fan, Yang, Ni, Dong, Zhang, Yu, Huang, Qingbo, Liu, Kan, Li, Xintao, Wang, Lei, Yao, Yuanxin, Ai, Qing, Zhang, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589559/
https://www.ncbi.nlm.nih.gov/pubmed/28903320
http://dx.doi.org/10.18632/oncotarget.10568
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author Gao, Yu
Li, Hongzhao
Ma, Xin
Fan, Yang
Ni, Dong
Zhang, Yu
Huang, Qingbo
Liu, Kan
Li, Xintao
Wang, Lei
Yao, Yuanxin
Ai, Qing
Zhang, Xu
author_facet Gao, Yu
Li, Hongzhao
Ma, Xin
Fan, Yang
Ni, Dong
Zhang, Yu
Huang, Qingbo
Liu, Kan
Li, Xintao
Wang, Lei
Yao, Yuanxin
Ai, Qing
Zhang, Xu
author_sort Gao, Yu
collection PubMed
description The E2F3 transcriptional regulatory pathway plays a major part in multiple-cancer progression, but the specific contributions of this pathway to tumor formation and the progression of clear cell renal cell carcinoma (ccRCC) are not fully understood. Clinically, we demonstrated that E2F3 was overexpressed in advanced tumor features. Moreover, cytoplasmic restoration predicted the poor overall survival of ccRCC patients. As a remarkable oncogene for ccRCC, high HIF-2α levels closely correlated with E2F3 upregulation. We observed in vitro that E2F3 overexpression and knockdown regulated HIF-2α expression. Furthermore, we found that HIF-2α harbored multiple E2F3 binding sites in the promoters. Mechanistically, E2F3 acted to transactivate HIF-2α transcription, which in turn exerted a serial effect on the pivotal epithelial–mesenchymal transition-related genes. The RNA interference-mediated silencing of HIF-2α attenuated E2F3-enhanced cell migration and invasion in vitro and in vivo. Overall, our results identified HIF-2α as a direct target gene for E2F3 upregulation, which was critical for carcinogenesis and progression of ccRCC. Thus, targeting the E2F3–HIF-2α interaction may be a promising approach to ccRCC treatment.
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spelling pubmed-55895592017-09-12 E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma Gao, Yu Li, Hongzhao Ma, Xin Fan, Yang Ni, Dong Zhang, Yu Huang, Qingbo Liu, Kan Li, Xintao Wang, Lei Yao, Yuanxin Ai, Qing Zhang, Xu Oncotarget Research Paper The E2F3 transcriptional regulatory pathway plays a major part in multiple-cancer progression, but the specific contributions of this pathway to tumor formation and the progression of clear cell renal cell carcinoma (ccRCC) are not fully understood. Clinically, we demonstrated that E2F3 was overexpressed in advanced tumor features. Moreover, cytoplasmic restoration predicted the poor overall survival of ccRCC patients. As a remarkable oncogene for ccRCC, high HIF-2α levels closely correlated with E2F3 upregulation. We observed in vitro that E2F3 overexpression and knockdown regulated HIF-2α expression. Furthermore, we found that HIF-2α harbored multiple E2F3 binding sites in the promoters. Mechanistically, E2F3 acted to transactivate HIF-2α transcription, which in turn exerted a serial effect on the pivotal epithelial–mesenchymal transition-related genes. The RNA interference-mediated silencing of HIF-2α attenuated E2F3-enhanced cell migration and invasion in vitro and in vivo. Overall, our results identified HIF-2α as a direct target gene for E2F3 upregulation, which was critical for carcinogenesis and progression of ccRCC. Thus, targeting the E2F3–HIF-2α interaction may be a promising approach to ccRCC treatment. Impact Journals LLC 2016-07-13 /pmc/articles/PMC5589559/ /pubmed/28903320 http://dx.doi.org/10.18632/oncotarget.10568 Text en Copyright: © 2017 Gao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Gao, Yu
Li, Hongzhao
Ma, Xin
Fan, Yang
Ni, Dong
Zhang, Yu
Huang, Qingbo
Liu, Kan
Li, Xintao
Wang, Lei
Yao, Yuanxin
Ai, Qing
Zhang, Xu
E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title_full E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title_fullStr E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title_full_unstemmed E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title_short E2F3 upregulation promotes tumor malignancy through the transcriptional activation of HIF-2α in clear cell renal cell carcinoma
title_sort e2f3 upregulation promotes tumor malignancy through the transcriptional activation of hif-2α in clear cell renal cell carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589559/
https://www.ncbi.nlm.nih.gov/pubmed/28903320
http://dx.doi.org/10.18632/oncotarget.10568
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