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Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line
Direct acting antiviral agents are emerging line of treatment to eradicate Hepatitis C virus. Recent controversy over whether direct acting antiviral agents increase rate of hepatocellular carcinoma in HCV patients or prevent it, has increased the need to elaborate underlying mechanisms on molecular...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256646/ https://www.ncbi.nlm.nih.gov/pubmed/35813116 http://dx.doi.org/10.1016/j.sjbs.2022.103332 |
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author | Atif, Muhammad Mustaan, Muhammad Abdul Falak, Sadia Ghaffar, Abdul Munir, Bushra |
author_facet | Atif, Muhammad Mustaan, Muhammad Abdul Falak, Sadia Ghaffar, Abdul Munir, Bushra |
author_sort | Atif, Muhammad |
collection | PubMed |
description | Direct acting antiviral agents are emerging line of treatment to eradicate Hepatitis C virus. Recent controversy over whether direct acting antiviral agents increase rate of hepatocellular carcinoma in HCV patients or prevent it, has increased the need to elaborate underlying mechanisms on molecular basis. This work was aimed to investigate the effect of sofosbuvir on the expression of selected oncogenes from the Ras/Raf/MEK/ERK pathway in Huh7 cell line. Results found concrete molecular evidence that sofosbuvir has significantly altered the expression of selected genes when huh7 cell line was treated with sofosbuvir. Nine genes related to HCC were found to be affected by sofosbuvir in a mixed effect manner. The relative expression of growth factors (VEGF, PDGFRB and HGF) was increased in sofosbuvir treated cell lines. The kinase family genes H-RAS, B-RAF, MET except MAPK1 were downregulated. Similarly, DUSP1 was upregulated and SPRY2 was slightly downregulated; both were negative feedback inhibitors of ERK signalling cascade. Sofosbuvir upregulated the growth factors and MAPK1 which suggests it to be a carcinogen. The downregulation of kinases and upregulation of DUSP1 make it an anticancer drug. Hence, the results from this study are important to prove that sofosbuvir neither reduce nor induce hepatocellular carcinoma. |
format | Online Article Text |
id | pubmed-9256646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92566462022-07-07 Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line Atif, Muhammad Mustaan, Muhammad Abdul Falak, Sadia Ghaffar, Abdul Munir, Bushra Saudi J Biol Sci Original Article Direct acting antiviral agents are emerging line of treatment to eradicate Hepatitis C virus. Recent controversy over whether direct acting antiviral agents increase rate of hepatocellular carcinoma in HCV patients or prevent it, has increased the need to elaborate underlying mechanisms on molecular basis. This work was aimed to investigate the effect of sofosbuvir on the expression of selected oncogenes from the Ras/Raf/MEK/ERK pathway in Huh7 cell line. Results found concrete molecular evidence that sofosbuvir has significantly altered the expression of selected genes when huh7 cell line was treated with sofosbuvir. Nine genes related to HCC were found to be affected by sofosbuvir in a mixed effect manner. The relative expression of growth factors (VEGF, PDGFRB and HGF) was increased in sofosbuvir treated cell lines. The kinase family genes H-RAS, B-RAF, MET except MAPK1 were downregulated. Similarly, DUSP1 was upregulated and SPRY2 was slightly downregulated; both were negative feedback inhibitors of ERK signalling cascade. Sofosbuvir upregulated the growth factors and MAPK1 which suggests it to be a carcinogen. The downregulation of kinases and upregulation of DUSP1 make it an anticancer drug. Hence, the results from this study are important to prove that sofosbuvir neither reduce nor induce hepatocellular carcinoma. Elsevier 2022-08 2022-06-01 /pmc/articles/PMC9256646/ /pubmed/35813116 http://dx.doi.org/10.1016/j.sjbs.2022.103332 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Atif, Muhammad Mustaan, Muhammad Abdul Falak, Sadia Ghaffar, Abdul Munir, Bushra Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title | Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title_full | Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title_fullStr | Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title_full_unstemmed | Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title_short | Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line |
title_sort | targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma ras/raf/mek/erk pathway in huh7 cell line |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256646/ https://www.ncbi.nlm.nih.gov/pubmed/35813116 http://dx.doi.org/10.1016/j.sjbs.2022.103332 |
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