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

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Teng Wu ◽  
Dongkun Zhang ◽  
Mingen Lin ◽  
Lihong Yu ◽  
Ting Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Colony Formation ◽  
Rna Polymerase Iii ◽  
Tumor Development ◽  
Related Factor ◽  
Survival Times ◽  
Lung Cancer Patients ◽  
High Level ◽  
Pol Iii

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.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mingen Lin ◽  
Chenghao Huang ◽  
Wenfeng Ren ◽  
Jun Chen ◽  
Ningshao Xia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Colony Formation ◽  
Rna Polymerase Iii ◽  
Tumor Development ◽  
5S Rrna ◽  
Trna Genes ◽  
Related Factor ◽  
Mechanism Analysis ◽  
Primary Mouse ◽  
Pol Iii

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.

scholarly journals Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chenghao Huang ◽  
Yanmei Zhang ◽  
Shuping Zhong
Keyword(s):  
Breast Cancer ◽  
Alcohol Consumption ◽  
Molecular Mechanism ◽  
Cell Transformation ◽  
Rna Polymerase Iii ◽  
Tumor Development ◽  
Epidemiological Studies ◽  
Tumor Formation ◽  
Related Factor ◽  
Pol Iii

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.

Identification of a new GLDC gene alternative splicing variant and its protumorigenic roles in lung cancer

2019 ◽  
Vol 15 (36) ◽  
pp. 4127-4139 ◽  
Author(s):  
Yingli Yuan ◽  
Luguo Sun ◽  
Xu Wang ◽  
Jingxian Chen ◽  
Mingnan Jia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Colony Formation ◽  
Lactate Production ◽  
Cellular Transformation ◽  
Lung Cancer Cell Line ◽  
Stem Cell Marker ◽  
Brdu Incorporation ◽  
Clinical Samples

Aim: To clarify the regulatory roles of GLDCV1, the first identified truncated glycine decarboxylase (GLDC), on cancer stem cells and tumorigenesis. Materials & methods: RT-PCR or RT-qPCR, immunoblotting and immunohistochemical staining were applied to assess gene expression. MTT, BrdU incorporation and colony formation assays were used to examine cell proliferation capacity. Soft agar colony formation and in vivo transplantation were applied to evaluate cellular transformation and tumorigenesis. Results & conclusion: Expression of GLDCV1 or GLDC was enhanced in non-small-cell lung cancer cell line and clinical samples. GLDCV1 overexpression induced MRC5 cell proliferation, transformation and tumorigenesis. Additionally, GLDCV1 increased lactate production and cancer stem cell marker expression and activated ERK and P38 pathways. Our study gained deeper insight into GLDC oncogene.

Down-regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis in Xuanwei Female Lung Cancer Patients

2015 ◽  
Vol 116 (6) ◽  
pp. 1007-1018 ◽  
Author(s):  
Yongchun Zhou ◽  
Xicai Wang ◽  
Yunchao Huang ◽  
Yan Chen ◽  
Guangqiang Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Lung Cancer Patients ◽  
Female Lung Cancer

Downregulation of Sulfiredoxin (Srx) Suppressed Cell Proliferation Migration and Invasion Through Inhibiting Extracellular Signal-Regulated Kinase/Nrf2 Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 11 (11) ◽  
pp. 2137-2145
Author(s):  
Xuejuan Zhu ◽  
Danqian Lu
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Related Factor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Nrf2 Signaling Pathway

Background: Sulfiredoxin (Srx) has been identified to play important roles in the development of various cancers. However, the precise effects and underlying mechanism of Srx on the progression of HCC are far from being fully understood. Materials and Methods: The abundances of Srx in THLE-2 cell and HCC cell lines were determined by western blot and RT-qPCR. Next, SK-Hep-1 cells were transfected with shRNA-Srx or shRNA-NC and treated with TBHQ (an extracellular signal-regulated kinase (ERK) activator) for functional experiments. Then, CCK8 and colony formation assays were used to determine cell proliferation and clone-forming abilities in vitro. Cell migration and invasion were assessed via wound healing and transwell assays. The expression of MMP2, MMP9 and key members in ERK/nuclear factor E2 related factor (Nrf2) signaling pathway was detected by performing western blot analysis. Results: We reported evidence that Srx was frequently up-regulated in HCC cell lines. Srx interference constrained cell proliferation, colony formation rate, migration and invasion of SK-Hep-1 cells. Moreover, mechanistic investigations indicated that Srx interference significantly inhibited the activation of ERK/Nrf2 signaling pathway, and ERK activator TBHQ can reverse the functions of Srx interference in SK-Hep-1 cells. Conclusion: Overall, Downregulation of Srx might impede HCC progression by suppressing ERK/Nrf2 signaling pathway. Findings in the current study reported the functional involvement and molecular mechanism of Srx in HCC, suggesting that Srx might have a potential therapeutic value in HCC treatment.

scholarly journals Effect of Lncrna FER1L4 Overexpression on Prognosis and Cell Proliferation in Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Xiang Jin ◽  
Xingang Liu ◽  
Huiqin Zhu ◽  
Yinghui Guan
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Size ◽  
Colony Formation ◽  
Small Cell ◽  
Normal Lung ◽  
Colony Formation Assay ◽  
Small Cell Lung ◽  
Over Expression ◽  
Favorable Prognosis

Abstract Background: The purpose of this study was to investigate the clinical significance and biological function of lncRNA FER1L4 in NSCLC. Methods: A total of 114 cases of NSCLC tissues and matched normal lung tissues were obtained from The first hospital of Jilin University between January 2009 and December 2016. The clinicopathological characteristics of patients were collected, including age, gender, tumor size, etc. The expression levels of LncRNA FER1L4 were detected by qRT-PCR. Non-small cell lung cancer cell lines (A549, H292 and H1299) were cultured with LncRNA FER1L4 mimics and LncRNA FER1L4 inhibitor. Cell proliferation was evaluated by CCK-8 and colony formation assay. Results: The expression levels of lncRNA FER1L4 were significantly lower in NSCLC tissues compared with those in matched normal lung tissues (P<0.05). Decreased level of lncRNA FER1L4 was significantly correlated with tumor size, TNM stage and lymph node metastasis (P<0.05). Moreover, lncRNA FER1L4 over-expression predicted favorable prognosis in NSCLC (P<0.05). Furthermore, CCK-8 and colony formation assay showed that lncRNA FER1L4 over-expression significantly suppressed cell proliferation. Conclusions: Our results suggested that LncRNA FER1L4 overexpression predicted favorable prognosis and suppressed cell proliferation in NSCLC, which may serve as a promising therapeutic target.

scholarly journals Cutting Edge: Regulatory T Cells from Lung Cancer Patients Directly Inhibit Autologous T Cell Proliferation

2002 ◽  
Vol 168 (9) ◽  
pp. 4272-4276 ◽  
Author(s):  
Edward Y. Woo ◽  
Heidi Yeh ◽  
Christina S. Chu ◽  
Katia Schlienger ◽  
Richard G. Carroll ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Cutting Edge ◽  
T Cell Proliferation ◽  
Lung Cancer Patients

scholarly journals Analysis of Prognostic and Therapeutic Values of Drug Resistance-Related Genes in the Lung Cancer Microenvironment

2021 ◽  
Author(s):  
Liang Zhu ◽  
Peixin Chen ◽  
Hao Wang ◽  
Lishu Zhao ◽  
Haoyue Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
T Cells ◽  
Significant Contribution ◽  
Tumor Development ◽  
Good Prognosis ◽  
Transcriptional Level ◽  
Lung Cancer Patients ◽  
Rna Polymerization ◽  
Cancer Tissues

Abstract Background: The interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance related genes, which affects the outcome of patients. CCDC73, DLGAP1, DSEL, ESR1, and SEC14L5 were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis.Results: The transcriptional expression level of DLGAP1 was remarkably increased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly decreased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes.Conclusions: Novel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.

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