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TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor. Ten-eleven translocation (TET) protein 2 (TET2), an evolutionarily conserved dioxygenases, is reported to be involved in various malignant tumor developments. Here, we aim to investigate the effect of TET2 on NPC progress in vit...

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Autores principales: Zhang, Xixia, Yang, Jing, Shi, Dong, Cao, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397601/
https://www.ncbi.nlm.nih.gov/pubmed/32774157
http://dx.doi.org/10.1186/s12935-020-01456-9
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author Zhang, Xixia
Yang, Jing
Shi, Dong
Cao, Zhiwei
author_facet Zhang, Xixia
Yang, Jing
Shi, Dong
Cao, Zhiwei
author_sort Zhang, Xixia
collection PubMed
description BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor. Ten-eleven translocation (TET) protein 2 (TET2), an evolutionarily conserved dioxygenases, is reported to be involved in various malignant tumor developments. Here, we aim to investigate the effect of TET2 on NPC progress in vitro and in vivo, and its detailed underlying mechanism. METHODS: Real-time PCR and western blotting were used to determine the expression levels of TET1/2/3 in NPC cell lines. The effects of TET2 on NPC progression were evaluated using CCK8 and invasion assays in vitro. Proteins interacted with TET2 in NPC cells were detected by immunoprecipitation and mass spectrometry. The effects of TET2 or pyruvate kinase, muscle (PKM) on glycolysis in NPC cells were examined by detecting glucose uptake and lactate production. The effects of TET2 on NPC progression were evaluated using xenograft tumor model in vivo. RESULTS: TET2 expression was decreased in NPC cells, and TET2 overexpression inhibited proliferation and invasion of NPC cells, which is independent on TET2’s catalytic activity. In mechanism, TET2 N-terminal domain interacts with PKM in cytoplasm to prevent PKM dimers from translocating into nucleus, suppressing glycolysis in NPC cells, thereby inhibiting proliferation and invasion of NPC cells. Moreover, using xenograft tumor model, we found that TET2 knockout promoted NPC progression and decreased survival rate. However, administration with the inhibitor of PKM, shikonin, decreased the tumor volume of TET2-cas9 group, and increased the survival rate. CONCLUSION: TET2 suppresses NPC development through interacting with PKM to inhibit glycolysis.
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spelling pubmed-73976012020-08-06 TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism Zhang, Xixia Yang, Jing Shi, Dong Cao, Zhiwei Cancer Cell Int Primary Research BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor. Ten-eleven translocation (TET) protein 2 (TET2), an evolutionarily conserved dioxygenases, is reported to be involved in various malignant tumor developments. Here, we aim to investigate the effect of TET2 on NPC progress in vitro and in vivo, and its detailed underlying mechanism. METHODS: Real-time PCR and western blotting were used to determine the expression levels of TET1/2/3 in NPC cell lines. The effects of TET2 on NPC progression were evaluated using CCK8 and invasion assays in vitro. Proteins interacted with TET2 in NPC cells were detected by immunoprecipitation and mass spectrometry. The effects of TET2 or pyruvate kinase, muscle (PKM) on glycolysis in NPC cells were examined by detecting glucose uptake and lactate production. The effects of TET2 on NPC progression were evaluated using xenograft tumor model in vivo. RESULTS: TET2 expression was decreased in NPC cells, and TET2 overexpression inhibited proliferation and invasion of NPC cells, which is independent on TET2’s catalytic activity. In mechanism, TET2 N-terminal domain interacts with PKM in cytoplasm to prevent PKM dimers from translocating into nucleus, suppressing glycolysis in NPC cells, thereby inhibiting proliferation and invasion of NPC cells. Moreover, using xenograft tumor model, we found that TET2 knockout promoted NPC progression and decreased survival rate. However, administration with the inhibitor of PKM, shikonin, decreased the tumor volume of TET2-cas9 group, and increased the survival rate. CONCLUSION: TET2 suppresses NPC development through interacting with PKM to inhibit glycolysis. BioMed Central 2020-08-03 /pmc/articles/PMC7397601/ /pubmed/32774157 http://dx.doi.org/10.1186/s12935-020-01456-9 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhang, Xixia
Yang, Jing
Shi, Dong
Cao, Zhiwei
TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title_full TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title_fullStr TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title_full_unstemmed TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title_short TET2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
title_sort tet2 suppresses nasopharyngeal carcinoma progression by inhibiting glycolysis metabolism
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397601/
https://www.ncbi.nlm.nih.gov/pubmed/32774157
http://dx.doi.org/10.1186/s12935-020-01456-9
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AT caozhiwei tet2suppressesnasopharyngealcarcinomaprogressionbyinhibitingglycolysismetabolism