scholarly journals The pattern of gene copy number variations (CNVs) in hepatocellular carcinoma; in silico analysis

2021 ◽  
Author(s):  
Arman Shahrisa ◽  
Maryam Tahmaseby ◽  
Hossein Ansari ◽  
Zahra Mohammadi ◽  
Vinicio Carloni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
In Silico ◽  
Tumor Suppressor Genes ◽  
Copy Number ◽  
Gene Copy ◽  
Suppressor Genes ◽  
Body Protein ◽  
Yin Yang 1 ◽  
Yin Yang

Abstract Recent studies showed that genetic lost or gain in the genome can predispose cells toward malignancy. Hepatocellular carcinoma (HCC) is the most common type of liver cancer which occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Prognosis of HCC is strongly connected with diagnostic delay. To date, no ideal screening modality has been developed for HCC. Recent findings demonstrated that Copy number variation (CNVs) can lead to activation of oncogenes and inactivation of tumor suppressor genes in cancers. In this study, CNV profile of 361 HCC samples was evaluated to reveal the potent - chromosomal regions involved in the disease. The obtained data showed that the chr1q and chr8p were two hotspot regions for gene amplifications and deletions in studied samples respectively. In this research, YY1AP1 (Yin Yang-1 Associated Protein 1) on chr1q22 was the most amplified gene in HCC samples and showed the positive correlation with tumor grade. Deletion of CHMP7 (Charged Multivesicular Body Protein 7) on chr8p21.3 was another frequently observed CNV among HCC patients. Both genes were interacted with variety of well-known oncogenes and tumor suppressor genes including YY1 (Yin Yang 1), CCND1 (Cyclin D1), HDAC1 (Histone deacetylase 1), VHL (von Hippel-Lindau tumor suppressor), MAD2L2 (Mitotic Arrest Deficient 2 Like 2), CEBPA (CCAAT/enhancer-binding protein alpha), CHMP4A, CHMP5, CHMP2A, CHMP3 and ENSG00000249884 (RNF103-CHMP3 gene), all of them are well-known in carcinogenesis. Although this study was based on in silico evaluations, our findings can open a new window for researchers of HCC to focus on such candidate genes during experimental assays.

scholarly journals The pattern of gene copy number variations (CNVs) in hepatocellular carcinoma; in silico analysis

2020 ◽  
Author(s):  
Hossein Ansari ◽  
Arman Shahrisa ◽  
Maryam Tahmaseby ◽  
Zahra Mohammadi ◽  
Vinicio Carloni ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
In Silico ◽  
Copy Number ◽  
In Silico Analysis ◽  
Multivesicular Body ◽  
Copy Number Variations ◽  
Molecular Networks ◽  
Gene Copy ◽  
Body Protein ◽  
Silico Analysis

Abstract Cancer-associated death is the second leading cause of death worldwide. Study of the involved molecular networks of cancers can identify the potential target for early diagnosis, efficient therapies, and predictive prognosis of patients with cancer. Copy number variations are one type of DNA mutations which has been connected with human cancers. The CNVs can be used to find the regions of the genome involved in cancer phenotypes. This study is aimed to perform genome-wide chromosomal CNVs in HCC samples to find hotspot regions of disease using in silico analysis. The obtained data showed that gain of chromosome 1q and loss of 8p were frequently observed in target cancerous tissues. All the gains and losses were associated with tumor grade and metastasis. However, the amplification of YY1AP1 (Yin Yang-1 Associated Protein 1) and deletion of CHMP7 (Charged Multivesicular Body Protein 7) were observed in most of patients. These expression levels of YY1AP1 and CHMP7 were also upregulated and downregulated in cancerous samples respectively. Additionally, these two genes interact with critical oncogene and tumor suppressor genes like MDM2 (Mouse double minute 2 homolog) and VHL (von Hippel-Lindau tumor suppressor) showing the potential of these genes in HCC pathogenesis. Based on the observed data we suggest the 1q and 8p as candidate regions for HCC for researches especially YY1AP1 and CHMP7 loci.

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.

scholarly journals The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Arman Shahrisa ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Ansari ◽  
Zahra Mohammadi ◽  
Vinicio Carloni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
In Silico ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Gene Copy Number ◽  
In Silico Analysis ◽  
Gene Copy ◽  
Sequencing Data ◽  
Silico Analysis

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. Results Our data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes. Conclusions Our in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.

scholarly journals An in silico integrative analysis of hepatocellular carcinoma omics databases shows the dual regulatory role of microRNAs either as tumor suppressors or as oncomirs

2021 ◽  
Author(s):  
Mahmoud M. Tolba ◽  
Bangli Soliman ◽  
Abdul Jabbar ◽  
HebaT'Allah Nasser ◽  
Mahmoud Elhefnawi
Keyword(s):  
Tumor Suppressor ◽  
In Silico ◽  
Tumor Suppressor Genes ◽  
Messenger Rna ◽  
Integrative Analysis ◽  
Suppressor Genes ◽  
Short Rnas ◽  
Genes Expression ◽  
Specific Mrnas ◽  
Mirnas Expression

MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untranslated region (3'UTR) of the messenger RNA to repress their functions. Recently, microRNAs have been widely used as a therapeutic approach for various types of Cancer. MicroRNA is categorized into tumor suppressor and oncomirs. Tumor suppressor microRNAs can repress the pathologically causative oncogenes of the hallmarks of Cancer. However, based on the fact that miRNA has no proper fidelity to bind specific mRNAs due to binding to off-targets, it results in a kind of inverse biological activity. Here, we have executed an in-silico integrative analysis of GEO/TCGA-LIHC of genes/microRNAs expression analysis in HCC, including (446 HCC vs. 146 normal specimens for miRNAs expression ) ad 488 specimens for genes expression. It virtually shows that microRNAs could have an ability to target both oncogenes and tumor suppressor genes that contribute to its dual activity role as a tumor suppressor and oncomirs via miRNA-lncRNA-TFs-PPI Crosstalk. Seven resultant microRNAs show a putative dual role in HCC. It enhances our concluded suggestion of using combination therapy of tumor suppressor genes activators with microRNAs.

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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