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Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteos...

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Autores principales: Shen, Shuying, Xu, Yining, Gong, Zhe, Yao, Teng, Qiao, Di, Huang, Yizhen, Zhang, Zhenlei, Gao, Jun, Ni, Haonan, Jin, Zhanping, Zhu, Yingchun, Wu, Hongfei, Wang, Qingxin, Fang, Xiangqian, Huang, Kangmao, Ma, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JKL International LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017158/
https://www.ncbi.nlm.nih.gov/pubmed/37008055
http://dx.doi.org/10.14336/AD.2022.0826
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author Shen, Shuying
Xu, Yining
Gong, Zhe
Yao, Teng
Qiao, Di
Huang, Yizhen
Zhang, Zhenlei
Gao, Jun
Ni, Haonan
Jin, Zhanping
Zhu, Yingchun
Wu, Hongfei
Wang, Qingxin
Fang, Xiangqian
Huang, Kangmao
Ma, Jianjun
author_facet Shen, Shuying
Xu, Yining
Gong, Zhe
Yao, Teng
Qiao, Di
Huang, Yizhen
Zhang, Zhenlei
Gao, Jun
Ni, Haonan
Jin, Zhanping
Zhu, Yingchun
Wu, Hongfei
Wang, Qingxin
Fang, Xiangqian
Huang, Kangmao
Ma, Jianjun
author_sort Shen, Shuying
collection PubMed
description Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.
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spelling pubmed-100171582023-04-01 Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism Shen, Shuying Xu, Yining Gong, Zhe Yao, Teng Qiao, Di Huang, Yizhen Zhang, Zhenlei Gao, Jun Ni, Haonan Jin, Zhanping Zhu, Yingchun Wu, Hongfei Wang, Qingxin Fang, Xiangqian Huang, Kangmao Ma, Jianjun Aging Dis Original Article Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression. JKL International LLC 2023-04-01 /pmc/articles/PMC10017158/ /pubmed/37008055 http://dx.doi.org/10.14336/AD.2022.0826 Text en copyright: © 2022 Shen et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Original Article
Shen, Shuying
Xu, Yining
Gong, Zhe
Yao, Teng
Qiao, Di
Huang, Yizhen
Zhang, Zhenlei
Gao, Jun
Ni, Haonan
Jin, Zhanping
Zhu, Yingchun
Wu, Hongfei
Wang, Qingxin
Fang, Xiangqian
Huang, Kangmao
Ma, Jianjun
Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title_full Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title_fullStr Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title_full_unstemmed Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title_short Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism
title_sort positive feedback regulation of circular rna hsa_circ_0000566 and hif-1α promotes osteosarcoma progression and glycolysis metabolism
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017158/
https://www.ncbi.nlm.nih.gov/pubmed/37008055
http://dx.doi.org/10.14336/AD.2022.0826
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