scholarly journals Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Cancers ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 8 ◽  
Author(s):  
Kwei-Yan Liu ◽  
Li-Ting Wang ◽  
Shih-Hsien Hsu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Chemical Sensor ◽  
Enzyme Level ◽  
Tumor Therapy ◽  
Tumor Formation ◽  
Current Evidence ◽  
Epigenetic Changes ◽  
Suppressor Genes

Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as TP53 and RB1.

Aberrant STAT1 methylation as a non-invasive biomarker in blood of HCV induced hepatocellular carcinoma

2021 ◽  
pp. 1-9
Author(s):  
Umaira Zakir ◽  
Nadir Naveed Siddiqui ◽  
Faizan-ul-Hassan Naqvi ◽  
Rizma Khan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Tumor Formation ◽  
Aberrant Methylation ◽  
Suppressor Genes ◽  
Non Invasive ◽  
Specific Pcr

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancer in the world and a reason behind different oncogenes activation and tumor suppressor genes inactivation. Hyper-methylation of tumor suppressor genes including RASSF1a, GSTP1, p16, and APC cause gene silencing as well as tumor cell invasion. STAT 1 gene is a part of signaling cascade of JAK/STAT and any dysregulation in signaling has been implicated in tumor formation. OBJECTIVE: The current investigation focus on the methylation role of STAT1 gene as a non-invasive biomarker in the progression and diagnosis of hepatocellular carcinoma. METHODS: STAT1 gene methylation status in 46 HCV induced hepatocellular carcinoma patients and 40 non-HCC controls were examined by methylation specific PCR. STAT1 gene expression was examined by real time PCR and further validated by various bioinformatics tools. RESULTS: STAT1 methylation in HCV-induced HCC (67.4%) was significantly higher compared to the non-HCC controls (p< 0.01). However, mRNA expression of STAT1 gene in methylated groups was significantly lower compared to unmethylated groups (p< 0.05). Furthermore, insilco analysis of STAT1 validated our results and shown expression of STAT1 mRNA was lower in liver cancer with the median 24.3 (p= 0.085). CONCLUSION: After using peripheral blood samples we observed that STAT1 silencing caused by aberrant methylation could be used as potential non-invasive biomarker for the diagnosis of HCV induced hepatocellular carcinoma. We conclude that blood as a sample source could be used instead of biopsy for early detection of HCC.

scholarly journals Transposon Mutagenesis-Guided CRISPR/Cas9 Screening Strongly Implicates Dysregulation of Hippo/YAP Signaling in Malignant Peripheral Nerve Sheath Tumor Development

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1584
Author(s):  
Germán L. Vélez-Reyes ◽  
Nicholas Koes ◽  
Ji Hae Ryu ◽  
Gabriel Kaufmann ◽  
Mariah Berner ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Cell Line ◽  
Schwann Cells ◽  
Tumor Suppressor Genes ◽  
Tumor Formation ◽  
Loss Of Function ◽  
Suppressor Genes ◽  
Nerve Sheath

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive, genomically complex, have soft tissue sarcomas, and are derived from the Schwann cell lineage. Patients with neurofibromatosis type 1 syndrome (NF1), an autosomal dominant tumor predisposition syndrome, are at a high risk for MPNSTs, which usually develop from pre-existing benign Schwann cell tumors called plexiform neurofibromas. NF1 is characterized by loss-of-function mutations in the NF1 gene, which encode neurofibromin, a Ras GTPase activating protein (GAP) and negative regulator of RasGTP-dependent signaling. In addition to bi-allelic loss of NF1, other known tumor suppressor genes include TP53, CDKN2A, SUZ12, and EED, all of which are often inactivated in the process of MPNST growth. A sleeping beauty (SB) transposon-based genetic screen for high-grade Schwann cell tumors in mice, and comparative genomics, implicated Wnt/β-catenin, PI3K-AKT-mTOR, and other pathways in MPNST development and progression. We endeavored to more systematically test genes and pathways implicated by our SB screen in mice, i.e., in a human immortalized Schwann cell-based model and a human MPNST cell line, using CRISPR/Cas9 technology. We individually induced loss-of-function mutations in 103 tumor suppressor genes (TSG) and oncogene candidates. We assessed anchorage-independent growth, transwell migration, and for a subset of genes, tumor formation in vivo. When tested in a loss-of-function fashion, about 60% of all TSG candidates resulted in the transformation of immortalized human Schwann cells, whereas 30% of oncogene candidates resulted in growth arrest in a MPNST cell line. Individual loss-of-function mutations in the TAOK1, GDI2, NF1, and APC genes resulted in transformation of immortalized human Schwann cells and tumor formation in a xenograft model. Moreover, the loss of all four of these genes resulted in activation of Hippo/Yes Activated Protein (YAP) signaling. By combining SB transposon mutagenesis and CRISPR/Cas9 screening, we established a useful pipeline for the validation of MPNST pathways and genes. Our results suggest that the functional genetic landscape of human MPNST is complex and implicate the Hippo/YAP pathway in the transformation of neurofibromas. It is thus imperative to functionally validate individual cancer genes and pathways using human cell-based models, to determinate their role in different stages of MPNST development, growth, and/or metastasis.

174 POSTER Epigenetic changes of tumor suppressor genes and therapeutic implications in glioblastoma

2008 ◽  
Vol 6 (12) ◽  
pp. 55-56
Author(s):  
L. Sooman ◽  
J. Gullbo ◽  
J. Lennartsson ◽  
S. Bergström ◽  
E. Blomquist ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Epigenetic Changes ◽  
Suppressor Genes ◽  
Therapeutic Implications

scholarly journals Epigenetic Changes in Tumor Suppressor Genes, P15, P16, APC-3 and E-cadherin in Body Fluid

2007 ◽  
Vol 23 (10) ◽  
pp. 498-503 ◽  
Author(s):  
Mei-Ling Chen ◽  
Julia Huei-Mei Chang ◽  
Kun-Tu Yeh ◽  
Ya-Sian Chang ◽  
Jan-Gowth Chang
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Body Fluid ◽  
Epigenetic Changes ◽  
Suppressor Genes ◽  
E Cadherin

scholarly journals P2-041: Epigenetic changes of the tumor suppressor genes SHP1, SHP2 SOCS1, SOCS3 and the transcription factor STAT1 in human lung cancer

2007 ◽  
Vol 2 (8) ◽  
pp. S506-S507
Author(s):  
Joachim Gullbo ◽  
Michael Bergqvist ◽  
Linda Sooman ◽  
Peter Ericsson ◽  
Johan Lennartsson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Epigenetic Changes ◽  
Suppressor Genes

ALV-J and REV synergistically activate a new oncogene of KIAA1199 via NF-κB and EGFR signaling regulated by miR-147

2018 ◽  
Author(s):  
Defang Zhou ◽  
Jingwen Xue ◽  
Pingping Zhuang ◽  
Xiyao Cui ◽  
Shuhai He ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Molecular Mechanism ◽  
Tumor Suppressor Genes ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Tumor Formation ◽  
Signalling Pathway ◽  
Suppressor Genes ◽  
Pathway Crosstalk ◽  
Pathogenic Effects

AbstractThe tumorigenesis is the result of the accumulation of multiple oncogenes and tumor suppressor genes changes. Co-infection of avian leucosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV), as two oncogenic retroviruses, showed synergistic pathogenic effects characterized by enhanced tumor initiation and progression. The molecular mechanism underlying synergistic effects of ALV-J and REV on the neoplasia remains unclear. Here, we found co-infection of ALV-J and REV enhanced the ability of virus infection, increased viral life cycle, maintained cell survival and enhanced tumor formation. We combined the high-throughput proteomic readout with a large-scale miRNA screening to identify which molecules are involved in the synergism. Our results revealed co-infection of ALV-J and REV activated a latent oncogene of KIAA1199 and inhibited the expression of tumor suppressor miR-147. Further, enhanced KIAA1199, down-regulated miR-147, activated NF-κB and EGFR were demonstrated in co-infected tissues and tumor. Mechanistically, we showed ALV-J and REV synergistically enhanced KIAA1199 by activation of NF-κB and EGFR signalling pathway, and the suppression of tumor suppressor miR-147 was contributed to maintain the NF-κB/KIAA1199/EGFR pathway crosstalk by targeting the 3’UTR region sequences of NF-κB p50 and KIAA1199. Our results contributed to the understanding of the molecular mechanisms of viral synergistic tumorgenesis, which provided the evidence that suggested the synergistic actions of two retroviruses could result in activation of latent pro-oncogenes.Author summaryThe tumorigenesis is the result of the accumulation of multiple oncogenes and tumor suppressor genes changes. Co-infection with ALV-J and REV showed synergistic pathogenic effects characterized by enhanced tumor progression, however, the molecular mechanism on the neoplasia remains unclear. Our results revealed co-infection of ALV-J and REV promotes tumorigenesis by both induction of a latent oncogene of KIAA1199 and suppression of the expression of tumor suppressor miR-147. Mechanistic studies revealed that ALV-J and REV synergistically enhance KIAA1199 by activation of NF-κB and EGFR signalling pathway, and the suppression of tumor suppressor miR-147 was contributed to maintain the NF-κB/KIAA1199/EGFR pathway crosstalk by targeting the 3’UTR region sequences of NF-κB p50 and KIAA1199. These results provided the evidence that suggested the synergistic actions of two retroviruses could result in activation of latent pro-oncogenes, indicating the potential preventive target and predictive factor for ALV-J and REV induced tumorigenesis.

Microsatellite Alterations of Major Tumor Suppressor Genes in Hepatocellular Carcinoma

2011 ◽  
Vol 7 (2) ◽  
pp. 96-107
Author(s):  
Jang Hyuk Seo ◽  
Doo Jin Kim ◽  
Seong Jin Cho ◽  
Ji Hyun Kwon ◽  
Eun Sook Nam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes
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