scholarly journals Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

2020 ◽  
Author(s):  
Lijuan Li ◽  
Shaohua Song ◽  
Xuailin Fang ◽  
Donglin Cao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Regulatory Networks ◽  
Macrophage Infiltration ◽  
Future Research ◽  
Activating Transcription Factor 3 ◽  
Poor Overall Survival ◽  
Basic Leucine Zipper ◽  
Atf3 Expression

Abstract Background: The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. Methods: We used UALCAN, ONCOMINE, Kaplan-Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC. Results: ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients. Conclusions: Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.

scholarly journals Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

2020 ◽  
Author(s):  
Lijuan Li ◽  
Shaohua Song ◽  
Xuailin Fang ◽  
Donglin Cao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Regulatory Networks ◽  
Macrophage Infiltration ◽  
Future Research ◽  
Activating Transcription Factor 3 ◽  
Poor Overall Survival ◽  
Basic Leucine Zipper ◽  
Atf3 Expression

Abstract Background: The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. Methods: We used UALCAN, ONCOMINE, Kaplan-Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC. Results: ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients. Conclusions: Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.

scholarly journals Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

2020 ◽  
Author(s):  
Lijuan Li ◽  
Shaohua Song ◽  
Xuailin Fang ◽  
Donglin Cao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Regulatory Networks ◽  
Macrophage Infiltration ◽  
Future Research ◽  
Activating Transcription Factor 3 ◽  
Poor Overall Survival ◽  
Basic Leucine Zipper ◽  
Atf3 Expression

Abstract Background The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear.Methods We used UALCAN, ONCOMINE, Kaplan-Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC.Results ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients.Conclusions Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.

scholarly journals Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lijuan Li ◽  
Shaohua Song ◽  
Xiaoling Fang ◽  
Donglin Cao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Regulatory Networks ◽  
Macrophage Infiltration ◽  
Future Research ◽  
Activating Transcription Factor 3 ◽  
Poor Overall Survival ◽  
Basic Leucine Zipper ◽  
Atf3 Expression

Abstract Background The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. Methods We used UALCAN, ONCOMINE, Kaplan–Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC. Results ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients. Conclusions Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.

scholarly journals PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma

2016 ◽  
Vol 40 (3-4) ◽  
pp. 757-769 ◽  
Author(s):  
Li Zhang ◽  
Guozhan Jia ◽  
Binya Shi ◽  
Guanqun Ge ◽  
Hongbin Duan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Hepg2 Cells ◽  
Tumour Growth ◽  
Xenograft Model ◽  
Tumour Suppressor ◽  
Poor Overall Survival

Background: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). Methods: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed. The role of PRSS8 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo. Results: PRSS8 mRNA and protein expression were decreased in most HCC tumours from that in matched adjacent non-tumour tissues. Low intratumoral PRSS8 expression was significantly correlated with poor overall survival (OS) in patients with HCC (P = 0.001). PRSS8 expression was an independent prognostic factor for OS (hazard ratio [HR] = 1.704, P = 0.009). Furthermore, restoring PRSS8 expression in high metastatic HCCLM3 cells significantly inhibited cell proliferation and invasion. In contrast, silencing PRSS8 expression in non-metastatic HepG2 cells significantly enhanced cell growth and invasion. Moreover, our in vivo data revealed that attenuated PRSS8 expression in HepG2 cells greatly promoted tumour growth, while overexpression of PRSS8 remarkably inhibited tumour growth in an HCCLM3 xenograft model. Enhanced cell growth and invasion ability mediated by the loss of PRSS8 expression was associated with downregulation of PTEN, Bax and E-cadherin and an upregulation in Bcl-2, MMP9 and N-cadherin. Conclusions: Our data demonstrate that PRSS8 may serve as a tumour suppressor in HCC progression, and represent a valuable prognostic marker and potential therapeutic target for HCC.

scholarly journals Prognostic biomarker SMARCC1 and its association with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaopeng Cai ◽  
Jiaming Zhou ◽  
Jingwen Deng ◽  
Zhi Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Tissue Microarray ◽  
Prognostic Value ◽  
Expression Profiles ◽  
Biological Significance ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Immune Infiltration

Abstract Background Epigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC. Methods The mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan–Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis. Results Through data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC. Conclusions SMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients.

scholarly journals Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium

2014 ◽  
Vol 306 (6) ◽  
pp. G474-G490 ◽  
Author(s):  
Boaz E. Aronson ◽  
Kelly A. Stapleton ◽  
Stephen D. Krasinski
Keyword(s):  
Transcription Factors ◽  
Intestinal Epithelium ◽  
Regulatory Networks ◽  
Small Intestinal Epithelium ◽  
Gata Factors ◽  
Evolution And Development ◽  
Multiple Context ◽  
Small Intestinal ◽  
Context Specific

The small intestinal epithelium develops from embryonic endoderm into a highly specialized layer of cells perfectly suited for the digestion and absorption of nutrients. The development, differentiation, and regeneration of the small intestinal epithelium require complex gene regulatory networks involving multiple context-specific transcription factors. The evolutionarily conserved GATA family of transcription factors, well known for its role in hematopoiesis, is essential for the development of endoderm during embryogenesis and the renewal of the differentiated epithelium in the mature gut. We review the role of GATA factors in the evolution and development of endoderm and summarize our current understanding of the function of GATA factors in the mature small intestine. We offer perspective on the application of epigenetics approaches to define the mechanisms underlying context-specific GATA gene regulation during intestinal development.

Abstract 4368: Differential Left versus Right Atrial Transcriptional Response to Angiotensin Stimulation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tal Hasin ◽  
Izhak Kehat ◽  
Ami Aronheim
Keyword(s):  
Transcription Factors ◽  
Left Atrium ◽  
Signaling Pathway ◽  
Right Atrial ◽  
Basic Leucine Zipper ◽  
Western Blots ◽  
Over Expression ◽  
Bzip Transcription Factors ◽  
Right Atria ◽  
Atf3 Expression

Introduction : Angiotensin stimulation is associated with atrial arrhythmias. Atrial fibrillation is commonly initiated in the left atrium. Cardiac over-expression of members of the angiotensin receptor signaling pathway correlates with atrial dilatation. Similarly cardiac over-expression of the inhibitory basic leucine zipper (bZIP) transcription factors JDP2 and ATF3 result in atrial dilatation. We have recently found a signaling pathway in which Angiotensin and Isoproterenol induce ATF3 experssion in the atria. Hypothesis : ATF3 expression may differ in left versus right atria. Methods and Results : mice were IP injected with Angiotensin, Isoproterenol or Saline. ATF3 expression in the left and right atria and in ventricles was analyzed using western blots and by immuno- histochemisty staining of paraffin embedded sections. Whereas Isoproterenol induced ATF3 expression in both atria and in ventricular tissue. Angiotensin induced ATF3 expression in the left atrium and in the ventricls but not in the right atrium (fig ). Analysis for other bZIP transcription factors revealed a responce to angiotensin in both atria. Conclusions and Implication : Angiotensin but not isoproterenol induces ATF3 expression differentially in the left but not right atria. To the best of our knowledge this is the first description of left atrial specific angiotensin mediated expression. This finding may be important in understanding atrial pathophysiological response to hemodynamic challenge and pathologies such as dilatation and generation of arrhythmia.

scholarly journals Up-regulated and interrelated expressions of GINS subunits predict poor prognosis in hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yi-Fan Lian ◽  
Shan-Shan Li ◽  
Yan-Lin Huang ◽  
Huan Wei ◽  
Dong-Mei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Poor Overall Survival ◽  
Patient Subgroup ◽  
Replicative Helicase ◽  
Kaplan Meier ◽  
Mcm Helicase ◽  
Elevated Expression ◽  
Core Components ◽  
Highly Correlated

The GINS complex is one of the core components of the eukaryotic replicative helicase CMG (Cdc45–MCM helicase–GINS) complex that serves as the replicative helicase unwinding duplex DNA ahead of moving replication fork during chromosome duplication. Many studies have highlighted the important functions amongst GINS subunits in various cancers. Nevertheless, the functions and prognostic roles of distinct GINS subunits in hepatocellular carcinoma (HCC) were largely unexplored. In the present study, we reported the prognostic values of GINS subunits in HCC patients through analysis of several databases, including Oncomine, (TCGA), and Kaplan–Meier Plotter (KMPlotter). We found that mRNA expressions of all GINS subunits were significantly up-regulated in HCC tumor than in non-tumor liver tissues. Survival analysis revealed that elevated expression of individual GINS subunit predicts a poor overall survival (OS) in all HCC patients. When sorting the patients by gender, the correlation between elevated expression of individual GINS subunit and poor OS remains significant in male patient subgroup, but not in female patient subgroup. Additionally, we found that co-overexpression of all GINS subunits was significantly associated with a higher hazard ratio, suggesting the GINS complex may co-operate to promote HCC progression. Indeed, their expressions were highly correlated with each other in the same cohort and TRANSFAC analysis revealed that four transcription factors including C/EBPα, Oct-1, Sp1, and USF may serve as common transcription factors binding to the promoters of all four GINS subunits. Therefore, we propose that individual GINS subunit or GINS complex as a whole could be potential prognostic biomarkers for HCC.

scholarly journals The Basic Leucine Zipper Transcription Factor PlBZP32 Associated with the Oxidative Stress Response Is Critical for Pathogenicity of the Lychee Downy Blight Oomycete Peronophythora litchii

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Guanghui Kong ◽  
Yubin Chen ◽  
Yizhen Deng ◽  
Dinan Feng ◽  
Liqun Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Leucine Zipper ◽  
Germination Rate ◽  
Hyphal Growth ◽  
Basic Leucine Zipper ◽  
Content Type ◽  
Bzip Transcription Factors ◽  
Rnai Technique

ABSTRACT Basic leucine zipper (bZIP) transcription factors are widespread in eukaryotes, including plants, animals, fungi, and oomycetes. However, the functions of bZIPs in oomycetes are rarely known. In this study, we identified a bZIP protein possessing a special bZIP-PAS structure in Peronophythora litchii, named PlBZP32. We found that PlBZP32 is upregulated in zoospores, in cysts, and during invasive hyphal growth. We studied the functions of PlBZP32 using the RNAi technique to suppress the expression of this gene. PlBZP32-silenced mutants were more sensitive to oxidative stress, showed a lower cyst germination rate, and produced more sporangia than the wild-type strain SHS3. The PlBZP32-silenced mutants were also less invasive on the host plant. Furthermore, we analyzed the activities of extracellular peroxidases and laccases and found that silencing PlBZP32 decreased the activities of P. litchii peroxidase and laccase. To our knowledge, this is the first report that the functions of a bZIP-PAS protein are associated with oxidative stress, asexual development, and pathogenicity in oomycetes. IMPORTANCE In this study, we utilized the RNAi technique to investigate the functions of PlBZP32, which possesses a basic leucine zipper (bZIP)-PAS structure, and provided insights into the contributions of bZIP transcription factors to oxidative stress, the production of sporangia, the germination of cysts, and the pathogenicity of Peronophythora litchii. This study also revealed the role of PlBZP32 in regulating the enzymatic activities of extracellular peroxidases and laccases in the plant-pathogenic oomycete.

scholarly journals A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5528
Author(s):  
Patrizia Perri ◽  
Mirco Ponzoni ◽  
Maria Valeria Corrias ◽  
Isabella Ceccherini ◽  
Simona Candiani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Target Genes ◽  
Genetic Alterations ◽  
Over Expression ◽  
Activating Mutations ◽  
Neuroblast Differentiation ◽  
Physiologic Role ◽  
Peripheral Sympathetic Nervous System

Neuroblastoma (NB) is a tumor of the peripheral sympathetic nervous system that substantially contributes to childhood cancer mortality. NB originates from neural crest cells (NCCs) undergoing a defective sympathetic neuronal differentiation and although the starting events leading to the development of NB remain to be fully elucidated, the master role of genetic alterations in key oncogenes has been ascertained: (1) amplification and/or over-expression of MYCN, which is strongly associated with tumor progression and invasion; (2) activating mutations, amplification and/or over-expression of ALK, which is involved in tumor initiation, angiogenesis and invasion; (3) amplification and/or over-expression of LIN28B, promoting proliferation and suppression of neuroblast differentiation; (4) mutations and/or over-expression of PHOX2B, which is involved in the regulation of NB differentiation, stemness maintenance, migration and metastasis. Moreover, altered microRNA (miRNA) expression takes part in generating pathogenetic networks, in which the regulatory loops among transcription factors, miRNAs and target genes lead to complex and aberrant oncogene expression that underlies the development of a tumor. In this review, we have focused on the circuitry linking the oncogenic transcription factors MYCN and PHOX2B with their transcriptional targets ALK and LIN28B and the tumor suppressor microRNAs let-7, miR-34 and miR-204, which should act as down-regulators of their expression. We have also looked at the physiologic role of these genetic and epigenetic determinants in NC development, as well as in terminal differentiation, with their pathogenic dysregulation leading to NB oncogenesis.

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