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Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes

TF IIB-related factor 1 (Brf1) is a key transcription factor of RNA polymerase III (Pol III) genes. Our early studies have demonstrated that Brf1 and Pol III genes are epigenetically modulated by histone H3 phosphorylation. Here, we have further investigated the relationship of the abnormal expressi...

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Autores principales: Wu, Teng, Zhang, Dongkun, Lin, Mingen, Yu, Lihong, Dai, Ting, Li, Shuai, Yu, Fenghai, Lu, Lei, Zheng, Liling, Zhong, Shuping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081602/
https://www.ncbi.nlm.nih.gov/pubmed/33995823
http://dx.doi.org/10.1155/2021/5554932
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author Wu, Teng
Zhang, Dongkun
Lin, Mingen
Yu, Lihong
Dai, Ting
Li, Shuai
Yu, Fenghai
Lu, Lei
Zheng, Liling
Zhong, Shuping
author_facet Wu, Teng
Zhang, Dongkun
Lin, Mingen
Yu, Lihong
Dai, Ting
Li, Shuai
Yu, Fenghai
Lu, Lei
Zheng, Liling
Zhong, Shuping
author_sort Wu, Teng
collection PubMed
description TF IIB-related factor 1 (Brf1) is a key transcription factor of RNA polymerase III (Pol III) genes. Our early studies have demonstrated that Brf1 and Pol III genes are epigenetically modulated by histone H3 phosphorylation. Here, we have further investigated the relationship of the abnormal expression of Brf1 with a high level of phosphorylated AMPKα (pAMPKα) and explored the role and molecular mechanism of pAMPKα-mediated dysregulation of Brf1 and Pol III genes in lung cancer. Brf1 is significantly overexpressed in lung cancer cases. The cases with high Brf1 expression display short overall survival times. Elevation of Brf1 expression is accompanied by a high level of pAMPKα. Brf1 and pAMPKα colocalize in nuclei. Further analysis indicates that the carcinogen MNNG induces pAMPKα to upregulate Brf1 expression, resulting in the enhancement of Pol III transcription. In contrast, inhibiting pAMPKα decreases cellular levels of Brf1, resulting in the reduction of Pol III gene transcription to attenuate the rates of cell proliferation and colony formation of lung cancer cells. These outcomes demonstrate that high Brf1 expression reveals a worse prognosis in lung cancer patients. pAMPKα-mediated dysregulation of Brf1 and Pol III genes plays important roles in cell proliferation, colony formation, and tumor development of lung cancer. Brf1 may be a biomarker for establishing the prognosis of lung cancer. It is a new mechanism that pAMPKα mediates dysregulation of Brf1 and Pol III genes to promote lung cancer development.
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spelling pubmed-80816022021-05-13 Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes Wu, Teng Zhang, Dongkun Lin, Mingen Yu, Lihong Dai, Ting Li, Shuai Yu, Fenghai Lu, Lei Zheng, Liling Zhong, Shuping Oxid Med Cell Longev Research Article TF IIB-related factor 1 (Brf1) is a key transcription factor of RNA polymerase III (Pol III) genes. Our early studies have demonstrated that Brf1 and Pol III genes are epigenetically modulated by histone H3 phosphorylation. Here, we have further investigated the relationship of the abnormal expression of Brf1 with a high level of phosphorylated AMPKα (pAMPKα) and explored the role and molecular mechanism of pAMPKα-mediated dysregulation of Brf1 and Pol III genes in lung cancer. Brf1 is significantly overexpressed in lung cancer cases. The cases with high Brf1 expression display short overall survival times. Elevation of Brf1 expression is accompanied by a high level of pAMPKα. Brf1 and pAMPKα colocalize in nuclei. Further analysis indicates that the carcinogen MNNG induces pAMPKα to upregulate Brf1 expression, resulting in the enhancement of Pol III transcription. In contrast, inhibiting pAMPKα decreases cellular levels of Brf1, resulting in the reduction of Pol III gene transcription to attenuate the rates of cell proliferation and colony formation of lung cancer cells. These outcomes demonstrate that high Brf1 expression reveals a worse prognosis in lung cancer patients. pAMPKα-mediated dysregulation of Brf1 and Pol III genes plays important roles in cell proliferation, colony formation, and tumor development of lung cancer. Brf1 may be a biomarker for establishing the prognosis of lung cancer. It is a new mechanism that pAMPKα mediates dysregulation of Brf1 and Pol III genes to promote lung cancer development. Hindawi 2021-04-20 /pmc/articles/PMC8081602/ /pubmed/33995823 http://dx.doi.org/10.1155/2021/5554932 Text en Copyright © 2021 Teng Wu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wu, Teng
Zhang, Dongkun
Lin, Mingen
Yu, Lihong
Dai, Ting
Li, Shuai
Yu, Fenghai
Lu, Lei
Zheng, Liling
Zhong, Shuping
Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title_full Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title_fullStr Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title_full_unstemmed Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title_short Exploring the Role and Mechanism of pAMPKα-Mediated Dysregulation of Brf1 and RNA Pol III Genes
title_sort exploring the role and mechanism of pampkα-mediated dysregulation of brf1 and rna pol iii genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081602/
https://www.ncbi.nlm.nih.gov/pubmed/33995823
http://dx.doi.org/10.1155/2021/5554932
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