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PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma

Phosphoglycerate mutase 1 (PGAM1) is a recently identified key catalytic enzyme in aerobic glycolysis. Recent literature has documented that dysregulated PGAM1 expression is associated with tumorigenesis in various cancers. However, the expression status and biological function of PGAM1 in non-small...

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Autores principales: Li, Fangfang, Yang, Hao, Kong, Tiandong, Chen, Shanshan, Li, Ping, Chen, Lu, Cheng, Jiuling, Cui, Guangying, Zhang, Guojun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453026/
https://www.ncbi.nlm.nih.gov/pubmed/32855383
http://dx.doi.org/10.1038/s41419-020-02900-4
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author Li, Fangfang
Yang, Hao
Kong, Tiandong
Chen, Shanshan
Li, Ping
Chen, Lu
Cheng, Jiuling
Cui, Guangying
Zhang, Guojun
author_facet Li, Fangfang
Yang, Hao
Kong, Tiandong
Chen, Shanshan
Li, Ping
Chen, Lu
Cheng, Jiuling
Cui, Guangying
Zhang, Guojun
author_sort Li, Fangfang
collection PubMed
description Phosphoglycerate mutase 1 (PGAM1) is a recently identified key catalytic enzyme in aerobic glycolysis. Recent literature has documented that dysregulated PGAM1 expression is associated with tumorigenesis in various cancers. However, the expression status and biological function of PGAM1 in non-small-cell lung cancer (NSCLC) are poorly elucidated. In this study, we found that PGAM1 was overexpressed in NSCLC tissues and that high expression of PGAM1 was associated with poor prognosis in NSCLC patients. Functionally, gain- and loss-of-function analysis showed that PGAM1 promoted proliferation and invasion in vitro, and facilitated tumor growth in vivo. Mechanistically, the transforming growth factor-β (TGF-β) signaling pathway was also markedly impaired in response to PGAM1 silencing. Additionally, we verified that PGAM1 was inhibited by miR-3614-5p via direct targeting of its 3’-untranslated regions in a hypoxia-independent manner. Furthermore, overexpression of miR-3614-5p attenuated NSCLC cell proliferation and invasion, and these effects could be partially reversed by reintroduction of PGAM1. Conclusively, our results suggest that the miR-3614-5p/PGAM1 axis plays a critical role during the progression of NSCLC, and these findings may provide a potential target for the development of therapeutic strategies for NSCLC patients.
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spelling pubmed-74530262020-09-03 PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma Li, Fangfang Yang, Hao Kong, Tiandong Chen, Shanshan Li, Ping Chen, Lu Cheng, Jiuling Cui, Guangying Zhang, Guojun Cell Death Dis Article Phosphoglycerate mutase 1 (PGAM1) is a recently identified key catalytic enzyme in aerobic glycolysis. Recent literature has documented that dysregulated PGAM1 expression is associated with tumorigenesis in various cancers. However, the expression status and biological function of PGAM1 in non-small-cell lung cancer (NSCLC) are poorly elucidated. In this study, we found that PGAM1 was overexpressed in NSCLC tissues and that high expression of PGAM1 was associated with poor prognosis in NSCLC patients. Functionally, gain- and loss-of-function analysis showed that PGAM1 promoted proliferation and invasion in vitro, and facilitated tumor growth in vivo. Mechanistically, the transforming growth factor-β (TGF-β) signaling pathway was also markedly impaired in response to PGAM1 silencing. Additionally, we verified that PGAM1 was inhibited by miR-3614-5p via direct targeting of its 3’-untranslated regions in a hypoxia-independent manner. Furthermore, overexpression of miR-3614-5p attenuated NSCLC cell proliferation and invasion, and these effects could be partially reversed by reintroduction of PGAM1. Conclusively, our results suggest that the miR-3614-5p/PGAM1 axis plays a critical role during the progression of NSCLC, and these findings may provide a potential target for the development of therapeutic strategies for NSCLC patients. Nature Publishing Group UK 2020-08-27 /pmc/articles/PMC7453026/ /pubmed/32855383 http://dx.doi.org/10.1038/s41419-020-02900-4 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Fangfang
Yang, Hao
Kong, Tiandong
Chen, Shanshan
Li, Ping
Chen, Lu
Cheng, Jiuling
Cui, Guangying
Zhang, Guojun
PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title_full PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title_fullStr PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title_full_unstemmed PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title_short PGAM1, regulated by miR-3614-5p, functions as an oncogene by activating transforming growth factor-β (TGF-β) signaling in the progression of non-small cell lung carcinoma
title_sort pgam1, regulated by mir-3614-5p, functions as an oncogene by activating transforming growth factor-β (tgf-β) signaling in the progression of non-small cell lung carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453026/
https://www.ncbi.nlm.nih.gov/pubmed/32855383
http://dx.doi.org/10.1038/s41419-020-02900-4
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