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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.
Afiliação
  • Wu T; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Zhang D; Department of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Lin M; The First Affiliated Hospital of Shantou University Medical College, China.
  • Yu L; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Dai T; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Li S; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Yu F; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Lu L; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Zheng L; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
  • Zhong S; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Oxid Med Cell Longev ; 2021: 5554932, 2021.
Article em En | MEDLINE | ID: mdl-33995823
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / RNA Polimerase III / Fatores Associados à Proteína de Ligação a TATA Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / RNA Polimerase III / Fatores Associados à Proteína de Ligação a TATA Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article