Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma

Lei, Junxia; Chen, Songlin; Zhong, Shuming

doi:10.1016/j.livres.2017.08.005

Cited by 16 publications

(15 citation statements)

References 116 publications

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“…[12][13][14][15]. Chronic alcohol consumption causes liver fibrosis and cirrhosis and enhances the risk of HCC [33]. Alcohol was classified as carcinogenic by the International Agency for Research on Cancer (IARC) [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…Decrease of Brf1 results in reduction of Pol III gene levels; the reduction is able to repress transformation of cells and xerography formation of the nude mouse [ 12 – 15 ]. Chronic alcohol consumption causes liver fibrosis and cirrhosis and enhances the risk of HCC [ 33 ]. Alcohol was classified as carcinogenic by the International Agency for Research on Cancer (IARC) [ 34 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Brf1 is a key factor which involves organ development [ 40 ]. Although our early studies have indicated that alcohol increases expression of Brf1 and Pol III genes of hepatocytes [ 7 , 33 ], it remains to be elucidated how alcohol affects Brf1 transcription. To deeply explore the mechanism of alcohol-affected Brf1 expression, we established the constructs of Brf1 promoter-luciferase reports of different lengths, such as p-760/+109bp, p-382/+109bp, and p-182/+109bp.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Alcohol feeding of mice promotes mammary tumorigenesis [36, 37]. Cell culture studies have demonstrated that the transcription products of RNA Pol III genes were elevated in both transformed and tumor cells [19, 20, 29, 33, 66–69], while the inductions of Pol III genes by alcohol in tumor cells were much higher than those in nontumor cells [33]. Consistent with this idea, enhanced Pol III gene transcription is required for oncogenic transformation of cells [19, 20, 29].…”

Section: Deregulation Of Rna Pol III Genes and Breast Cancermentioning

confidence: 99%

Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer

Huang

Zhang

Zhong

2019

Oxidative Medicine and Cellular Longevity

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Breast cancer is the most common malignant disease of females. Overall, one woman in every nine will get breast cancer at some time in her life. Epidemiological studies have indicated that alcohol consumption has most consistently been associated with breast cancer risk. However, the mechanism of alcohol-associated breast cancer remains to be addressed. Little is known about the effects of alcohol consumption on Brf1 (TFIIIB-related factor 1) expression and RNA Pol III gene (RNA polymerase III-dependent gene) transcription, which are responsible for protein synthesis and tightly linked to cell proliferation, cell transformation, and tumor development. Emerging evidences have indicated that alcohol induces deregulation of Brf1 and Pol III genes to cause the alterations of cell phenotypes and tumor formation. In this paper, we summarize the progresses regarding alcohol-caused increase in the expression of Brf1 and Pol III genes and analysis of its molecular mechanism of breast cancer. As the earlier and accurate diagnosis approach of breast cancer is not available yet, exploring the molecular mechanism and identifying the biomarker of alcohol-associated breast cancer are especially important. Recent studies have demonstrated that Brf1 is overexpressed in most ER+ (estrogen receptor positive) cases of breast cancer and the change in cellular levels of Brf1 reflects the therapeutic efficacy and prognosis of this disease. It suggests that Brf1 may be a potential diagnosis biomarker and a therapeutic target of alcohol-associated breast cancer.

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“…During cell cycle, the transcription of RNA pol III is regulated to ensure normal cellular growth ( 10 , 11 ). Previous studies reported that RNA pol III activity plays a key role in the deregulation of a variety of cancers, regardless of tissue types ( 12 , 13 ). Deregulation of TFIIIB-mediated transcription is an important factor in tumor development ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Silencing of BRF2 inhibits the growth and metastasis of lung cancer cells

Bian

Pan

2020

Mol Med Rep

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Transcription factor II B (TFIIB)-related factor 2 (BRF2) is involved in the development of cancer, but its role in lung cancer is underreported. The present study aimed to explore the role of BRF2 in the regulation of lung cancer cells. Immunofluorescence staining and immunohistochemistry were performed to detect BRF2 protein expression in human lung cancer cells and tissues. Following cell transfection with small interfering RNA for silencing BRF2, the cell proliferation was examined by Cell Counting Kit-8 and MTT assays. Cell apoptosis, migration and invasion were determined by flow cytometry, wound-healing and Transwell assay. The expression levels of Akt, phosphorylated (p)-Akt, Bax, E-cadherin, Bcl-2, N-cadherin, Snail and epidermal growth factor receptor (EGFR) in human lung cancer A549 cells were detected by western blotting. The results demonstrated that BRF2 expression was increased in human lung cancer cells and tissues, and that silencing of BRF2 promoted cell apoptosis but inhibited cell proliferation and migration. The protein expression levels of Akt, E-cadherin, p-Akt, Bcl-2, N-cadherin, Snail and EGFR in A549 cells were inhibited by silencing of BRF2, while expression levels of Bax and E-cadherin were increased by silencing BRF2. In conclusion, BRF2 demonstrates high expression in lung cancer and silencing of BRF2 inhibits the growth and metastasis of lung cancer cells. The current findings provide a novel approach for the treatment of lung cancer.

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Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma

Cited by 16 publications

References 116 publications

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

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

Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer

Silencing of BRF2 inhibits the growth and metastasis of lung cancer cells

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