{"title":"Polymorphic Variants of <i>ASS1</i> Gene Related to Arginine Metabolism and the Risk of HCC.","authors":"Kulsoom Bibi, Tehseen Fatima, Saba Sohrab, Ghulam Haider, Shamshad Zarina, Amber Ilyas","doi":"10.2174/0929866530666230529143121","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.</p><p><strong>Objectives: </strong>The aim of this study is to analyze the <i>ASS1</i> gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.</p><p><strong>Method: </strong>Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of <i>ASS1</i> gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between <i>ASS1</i> gene with other associated gene/proteins.</p><p><strong>Results: </strong>The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in <i>ASS1</i> and <i>NOS2</i> genes was observed. Bioinformatics analysis reveals the correlation between <i>ASS1</i> polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.</p><p><strong>Conclusion: </strong>Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of <i>ASS1</i> might be helpful in early diagnostic and therapeutic purposes.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein and Peptide Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0929866530666230529143121","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.
Objectives: The aim of this study is to analyze the ASS1 gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.
Method: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of ASS1 gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between ASS1 gene with other associated gene/proteins.
Results: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in ASS1 and NOS2 genes was observed. Bioinformatics analysis reveals the correlation between ASS1 polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.
Conclusion: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of ASS1 might be helpful in early diagnostic and therapeutic purposes.
期刊介绍：
Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations.
Protein & Peptide Letters focuses on:
Structure Studies
Advances in Recombinant Expression
Drug Design
Chemical Synthesis
Function
Pharmacology
Enzymology
Conformational Analysis
Immunology
Biotechnology
Protein Engineering
Protein Folding
Sequencing
Molecular Recognition
Purification and Analysis
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