The significance of Runx2 mediating alcohol-induced Brf1 expression and RNA Pol III gene transcription

Hong, Zaifa; Zeng, Fang; Lei, Junxia; Shi, Guo‐Ming; Zhang, Yanmei; He, Zhiming; b., Wen Li; Zhong, Shuming

doi:10.1016/j.cbi.2020.109057

Cited by 8 publications

(22 citation statements)

References 47 publications

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“…We performed immunohistochemical staining with Brf1 antibody (1 : 200). Its details were described in our previous study [ 20 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

“…The levels of Brf1 immunostaining were evaluated independently by two pathologists who were blinded to the survival outcomes of the participants based on the proportion of positively stained tumor cells (stain area) and the intensity of staining [ 20 ]. The immunostaining results were performed by multiplying the staining intensity by the stained area (staining index (SI)) as previously described [ 30 , 36 , 37 ]. The Brf1 expression levels in lung cancer lesions were determined by the SI, which was 0, 1, 2, 3, 4, 6, 9, or 12.…”

Section: Methodsmentioning

confidence: 99%

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

Zhang

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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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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“…We performed immunohistochemical staining with Brf1 antibody (1 : 200). Its details were described in our previous study [ 20 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Zhang

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…101 Runx2 is a transcription factor that plays a key regulatory role in osteoblast differentiation. 102,103 DNA sequencing found that the receptor activator of nuclear factor kB ligand (RANKL) contains a Runx2 binding site in the promoter region. 40,104 Thus, αvβ3-induced bone matrix dissolution likely depends on the delivery of Runx2 to the nucleus to promote RANKL transcription.…”

Section: The αVβ3/runx2/rankl Pathway Is Closely Related To Osteolytimentioning

confidence: 99%

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Tang¹,

Xu²,

Zhang³

et al. 2020

OTT

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In prostate cancer, distant organ metastasis is the leading cause of patient death. Although the mechanism of malignant tumor metastasis is unclear, studies have confirmed that integrin αVβ3 plays an important role in this process. In prostate cancer, αVβ3 mediates adhesion, invasion, immune escape and neovascularization through interactions with different ligands. Among these ligands and in addition to proteins that are directly related to tumor invasion, other proteins that contain the RGD structure could also bind to αVβ3 and cause a number of biological effects. In this article, we summarized the ligand and downstream proteins related to αVβ3-mediated prostate cancer metastasis as well as some diagnostic and therapeutic measures targeting αVβ3.

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“…The endogenous peroxidase activity was quenched by 3% hydrogen peroxide for 15 minutes. The sections were incubated with primary antibody, Brf1 (1 : 200) rabbit antibody, overnight at 4°C [32]. Then, the tissue sections were sequentially incubated with ready to use HRP-immunoglobulin (EnVision™) for 30 min and were developed with 3,3 ′ -diaminobenzidine (DAB) as a chromogen substrate.…”

Section: Cell Proliferation and Colony Formation Approximately 2 × 10mentioning

confidence: 99%

“…Then, the tissue sections were sequentially incubated with ready to use HRP-immunoglobulin (EnVision™) for 30 min and were developed with 3,3 ′ -diaminobenzidine (DAB) as a chromogen substrate. The nuclei were counterstained with Meyer's hematoxylin [16,32].…”

Section: Cell Proliferation and Colony Formation Approximately 2 × 10mentioning

confidence: 99%

Mitogen- and Stress-Activated Protein Kinase 1 Mediates Alcohol-Upregulated Transcription of Brf1 and tRNA Genes to Cause Phenotypic Alteration

Lin

Huang

Ren

et al. 2020

Oxidative Medicine and Cellular Longevity

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Upregulation of Brf1 (TFIIB-related factor 1) and Pol III gene (RNA polymerase III-dependent gene, such as tRNAs and 5S rRNA) activities is associated with cell transformation and tumor development. Alcohol intake causes liver injury, such as steatosis, inflammation, fibrosis, and cirrhosis, which enhances the risk of HCC development. However, the mechanism of alcohol-promoted HCC remains to be explored. We have designed the complementary research system, which is composed of cell lines, an animal model, human samples, and experiments in vivo and in vitro, to carry out this project by using molecular biological, biochemical, and cellular biological approaches. It is a unique system to explore the mechanism of alcohol-associated HCC. Our results indicate that alcohol upregulates Brf1 and Pol III gene (tRNAs and 5S rRNA) transcription in primary mouse hepatocytes, immortalized mouse hepatocyte-AML-12 cells, and engineered human HepG2-ADH cells. Alcohol activates MSK1 to upregulate expression of Brf1 and Pol III genes, while inhibiting MSK1 reduces transcription of Brf1 and Pol III genes in alcohol-treated cells. The inhibitor of MSK1, SB-747651A, decreases the rates of cell proliferation and colony formation. Alcohol feeding promotes liver tumor development of the mouse. These results, for the first time, show the identification of the alcohol-response promoter fragment of the Pol III gene key transcription factor, Brf1. Our studies demonstrate that Brf1 expression is elevated in HCC tumor tissues of mice and humans. Alcohol increases cellular levels of Brf1, resulting in enhancement of Pol III gene transcription in hepatocytes through MSK1. Our mechanism analysis has demonstrated that alcohol-caused high-response fragment of the Brf1 promoter is at p-382/+109bp. The MSK1 inhibitor SB-747651A is an effective reagent to repress alcohol-induced cell proliferation and colony formation, which is a potential pharmaceutical agent. Developing this inhibitor as a therapeutic approach will benefit alcohol-associated HCC patients.

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The significance of Runx2 mediating alcohol-induced Brf1 expression and RNA Pol III gene transcription

Cited by 8 publications

References 47 publications

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

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

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Mitogen- and Stress-Activated Protein Kinase 1 Mediates Alcohol-Upregulated Transcription of Brf1 and tRNA Genes to Cause Phenotypic Alteration

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