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Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma

BACKGROUND: The protein kinase C (PKC) family of serine/threonine kinases contains more than ten isozymes that are involved in multiple signaling pathways, including cell cycle regulation and carcinogenesis. The PKCε isozyme is an oncogene known to be upregulated in various signaling pathways involv...

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Autores principales: Rehman, Areeba, Shabbir, Maria, Badshah, Yasmin, Khan, Khushbukhat, Trembley, Janeen H., Ashraf, Naeem Mahmood, Afsar, Tayyaba, Almajwal, Ali, Alruwaili, Nawaf W., Alshamari, Ali, Alanezi, Tariq Nahar, Razak, Suhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926771/
https://www.ncbi.nlm.nih.gov/pubmed/36782184
http://dx.doi.org/10.1186/s12885-023-10618-7
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author Rehman, Areeba
Shabbir, Maria
Badshah, Yasmin
Khan, Khushbukhat
Trembley, Janeen H.
Ashraf, Naeem Mahmood
Afsar, Tayyaba
Almajwal, Ali
Alruwaili, Nawaf W.
Alshamari, Ali
Alanezi, Tariq Nahar
Razak, Suhail
author_facet Rehman, Areeba
Shabbir, Maria
Badshah, Yasmin
Khan, Khushbukhat
Trembley, Janeen H.
Ashraf, Naeem Mahmood
Afsar, Tayyaba
Almajwal, Ali
Alruwaili, Nawaf W.
Alshamari, Ali
Alanezi, Tariq Nahar
Razak, Suhail
author_sort Rehman, Areeba
collection PubMed
description BACKGROUND: The protein kinase C (PKC) family of serine/threonine kinases contains more than ten isozymes that are involved in multiple signaling pathways, including cell cycle regulation and carcinogenesis. The PKCε isozyme is an oncogene known to be upregulated in various signaling pathways involved in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC). However, there is no known association of missense SNPs in PKCε with this disease, which can be a potential biomarker for early diagnosis and treatment. This research reveals a novel missense SNP in PKCε that is associated with HCV-induced HCC in the Pakistani population. METHODS: The PKCε SNP with amino acid substitution of E14K was chosen for wet lab analysis. Tetra ARMS-PCR was employed for the identification of high-risk SNP in PKCε of HCV-induced HCC patients. Liver function testing was also performed for comparison between the liver condition of the HCC patient and control group, and the viral load of HCC patient samples was evaluated to determine any alteration in the viral infectivity between different genotypes of the selected high-risk PKCε variant SNP. RESULTS: Frequency distribution of the homozygous GG genotype was found to be highest among HCV-induced HCC patients and was also found to be significantly associated with disease development and progression. The p values of comparative data obtained for the other two genotypes, heterozygous AG and homozygous AA, of the SNP also showed the significance of the data for these alleles. Still, their odds ratio and relative risk analysis did not indicate their association with HCV-induced HCC. CONCLUSION: The distribution of a genotype GG of PKCε has been found in HCV- induced HCC patients. Therefore, these PKCε SNP have the potential to be biomarkers for HCV-induced HCC. Further investigation using a larger sample size would provide additional insight into these initial data and open a new avenue for a better prognosis of this disease.
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spelling pubmed-99267712023-02-15 Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma Rehman, Areeba Shabbir, Maria Badshah, Yasmin Khan, Khushbukhat Trembley, Janeen H. Ashraf, Naeem Mahmood Afsar, Tayyaba Almajwal, Ali Alruwaili, Nawaf W. Alshamari, Ali Alanezi, Tariq Nahar Razak, Suhail BMC Cancer Research BACKGROUND: The protein kinase C (PKC) family of serine/threonine kinases contains more than ten isozymes that are involved in multiple signaling pathways, including cell cycle regulation and carcinogenesis. The PKCε isozyme is an oncogene known to be upregulated in various signaling pathways involved in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC). However, there is no known association of missense SNPs in PKCε with this disease, which can be a potential biomarker for early diagnosis and treatment. This research reveals a novel missense SNP in PKCε that is associated with HCV-induced HCC in the Pakistani population. METHODS: The PKCε SNP with amino acid substitution of E14K was chosen for wet lab analysis. Tetra ARMS-PCR was employed for the identification of high-risk SNP in PKCε of HCV-induced HCC patients. Liver function testing was also performed for comparison between the liver condition of the HCC patient and control group, and the viral load of HCC patient samples was evaluated to determine any alteration in the viral infectivity between different genotypes of the selected high-risk PKCε variant SNP. RESULTS: Frequency distribution of the homozygous GG genotype was found to be highest among HCV-induced HCC patients and was also found to be significantly associated with disease development and progression. The p values of comparative data obtained for the other two genotypes, heterozygous AG and homozygous AA, of the SNP also showed the significance of the data for these alleles. Still, their odds ratio and relative risk analysis did not indicate their association with HCV-induced HCC. CONCLUSION: The distribution of a genotype GG of PKCε has been found in HCV- induced HCC patients. Therefore, these PKCε SNP have the potential to be biomarkers for HCV-induced HCC. Further investigation using a larger sample size would provide additional insight into these initial data and open a new avenue for a better prognosis of this disease. BioMed Central 2023-02-13 /pmc/articles/PMC9926771/ /pubmed/36782184 http://dx.doi.org/10.1186/s12885-023-10618-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Rehman, Areeba
Shabbir, Maria
Badshah, Yasmin
Khan, Khushbukhat
Trembley, Janeen H.
Ashraf, Naeem Mahmood
Afsar, Tayyaba
Almajwal, Ali
Alruwaili, Nawaf W.
Alshamari, Ali
Alanezi, Tariq Nahar
Razak, Suhail
Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title_full Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title_fullStr Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title_full_unstemmed Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title_short Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma
title_sort elucidating the role of missense snp of protein kinase c epsilon in hcv-induced hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926771/
https://www.ncbi.nlm.nih.gov/pubmed/36782184
http://dx.doi.org/10.1186/s12885-023-10618-7
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