Cargando…
Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis
Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental st...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550071/ https://www.ncbi.nlm.nih.gov/pubmed/36215278 http://dx.doi.org/10.1371/journal.pone.0275834 |
_version_ | 1784805810027626496 |
---|---|
author | Badshah, Yasmin Shabbir, Maria Khan, Khushbukhat Fatima, Maha Majoka, Iqra Aslam, Laiba Munawar, Huda |
author_facet | Badshah, Yasmin Shabbir, Maria Khan, Khushbukhat Fatima, Maha Majoka, Iqra Aslam, Laiba Munawar, Huda |
author_sort | Badshah, Yasmin |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGFβ-1 +29C/T and IL-6–174 G/C polymorphisms in HCV-induced HCC. AliBaba2 was used to predict the effect of IL-6–174 G/C on transcription factor binding site in IL-6 gene. Structural changes in the mutant TGFβ-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGFβ-1 +29C/T genotypes in HCC and control subjects, amplification refractory mutation system PCR (ARMS-PCR) was performed on 213 HCC and 216 control samples. GraphPad Prism version 8.0 was used for the statistical analysis of the results. In-silico analysis revealed the regulatory nature of both IL-6 -174G/C and TGFβ-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGFβ-1 gene have an increased risk of developing HCC (p<0.0001, OR = 5.403, RR = 2.062) as compared to individuals with CT and CC genotype. Similarly, GC genotype carriers for IL-6 gene exhibit an increased risk of HCC susceptibility (p<0.0001, OR = 2.276, RR = 1.512) as compared to the people carrying the GG genotype. Genotype TT of TGFβ-1 gene and genotype GC of IL-6 gene are found to be associated with HCV-induced HCC. IL-6 polymorphism may alter its transcription that leads to its pathogenicity. TGFβ-1 polymorphism may alter protein structure stability. |
format | Online Article Text |
id | pubmed-9550071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95500712022-10-11 Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis Badshah, Yasmin Shabbir, Maria Khan, Khushbukhat Fatima, Maha Majoka, Iqra Aslam, Laiba Munawar, Huda PLoS One Research Article Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGFβ-1 +29C/T and IL-6–174 G/C polymorphisms in HCV-induced HCC. AliBaba2 was used to predict the effect of IL-6–174 G/C on transcription factor binding site in IL-6 gene. Structural changes in the mutant TGFβ-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGFβ-1 +29C/T genotypes in HCC and control subjects, amplification refractory mutation system PCR (ARMS-PCR) was performed on 213 HCC and 216 control samples. GraphPad Prism version 8.0 was used for the statistical analysis of the results. In-silico analysis revealed the regulatory nature of both IL-6 -174G/C and TGFβ-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGFβ-1 gene have an increased risk of developing HCC (p<0.0001, OR = 5.403, RR = 2.062) as compared to individuals with CT and CC genotype. Similarly, GC genotype carriers for IL-6 gene exhibit an increased risk of HCC susceptibility (p<0.0001, OR = 2.276, RR = 1.512) as compared to the people carrying the GG genotype. Genotype TT of TGFβ-1 gene and genotype GC of IL-6 gene are found to be associated with HCV-induced HCC. IL-6 polymorphism may alter its transcription that leads to its pathogenicity. TGFβ-1 polymorphism may alter protein structure stability. Public Library of Science 2022-10-10 /pmc/articles/PMC9550071/ /pubmed/36215278 http://dx.doi.org/10.1371/journal.pone.0275834 Text en © 2022 Badshah et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Badshah, Yasmin Shabbir, Maria Khan, Khushbukhat Fatima, Maha Majoka, Iqra Aslam, Laiba Munawar, Huda Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title | Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title_full | Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title_fullStr | Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title_full_unstemmed | Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title_short | Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis |
title_sort | manipulation of interleukin-6 (il-6) and transforming growth factor beta-1(tgfβ-1) towards viral induced liver cancer pathogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550071/ https://www.ncbi.nlm.nih.gov/pubmed/36215278 http://dx.doi.org/10.1371/journal.pone.0275834 |
work_keys_str_mv | AT badshahyasmin manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT shabbirmaria manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT khankhushbukhat manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT fatimamaha manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT majokaiqra manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT aslamlaiba manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis AT munawarhuda manipulationofinterleukin6il6andtransforminggrowthfactorbeta1tgfb1towardsviralinducedlivercancerpathogenesis |