DNA methylation of human choline kinase alpha gene

Increased level of choline kinase (CK) is a common feature in cancers and inhibition of this enzyme has been applied as anticancer strategy. DNA methylation of gene promoter especially at CpG island is associated with suppression of gene expression. Despite the importance of CK especially the alpha...

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Main Authors: Siti Aisyah Faten Mohamed Sa'dom, Nur Farah Hani Azemi, Mohammad Shahrizal Mohammad Umar, Yoke, Hiang Yee, Wei, Cun See Too, Ling, Ling Few
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2020
Online Access:http://journalarticle.ukm.my/14747/1/ARTIKEL%2020.pdf
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author Siti Aisyah Faten Mohamed Sa'dom,
Nur Farah Hani Azemi,
Mohammad Shahrizal Mohammad Umar,
Yoke, Hiang Yee
Wei, Cun See Too
Ling, Ling Few
author_facet Siti Aisyah Faten Mohamed Sa'dom,
Nur Farah Hani Azemi,
Mohammad Shahrizal Mohammad Umar,
Yoke, Hiang Yee
Wei, Cun See Too
Ling, Ling Few
author_sort Siti Aisyah Faten Mohamed Sa'dom,
collection UKM
description Increased level of choline kinase (CK) is a common feature in cancers and inhibition of this enzyme has been applied as anticancer strategy. DNA methylation of gene promoter especially at CpG island is associated with suppression of gene expression. Despite the importance of CK especially the alpha isoform in cancer pathogenesis, epigenetic regulation of ckα expression has not been investigated. Hence, this study aimed to determine the effect of DNA methylation on ckα promoter activity and gene expression by using hypomethylating (5-aza) and methylating (budesonide) agents. The level of DNA methylation in the second CpG island of ckα promoter was determined by PCR-based method. 5-aza and budesonide increased the methylation of the selected CpG island compared to untreated control. Treatment with the drugs produced opposite effect, with 5-aza induced ckα promoter activity and gene expression while budesonide suppressed the promoter activity and mRNA level of this gene. Deletion of a region containing the second CpG island on ckα promoter resulted in significantly lower promoter activity. In conclusion, this study showed that DNA methylation could be one of the mechanisms that regulate the expression of ckα gene.
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spelling ukm.eprints-147472020-06-17T08:14:29Z http://journalarticle.ukm.my/14747/ DNA methylation of human choline kinase alpha gene Siti Aisyah Faten Mohamed Sa'dom, Nur Farah Hani Azemi, Mohammad Shahrizal Mohammad Umar, Yoke, Hiang Yee Wei, Cun See Too Ling, Ling Few Increased level of choline kinase (CK) is a common feature in cancers and inhibition of this enzyme has been applied as anticancer strategy. DNA methylation of gene promoter especially at CpG island is associated with suppression of gene expression. Despite the importance of CK especially the alpha isoform in cancer pathogenesis, epigenetic regulation of ckα expression has not been investigated. Hence, this study aimed to determine the effect of DNA methylation on ckα promoter activity and gene expression by using hypomethylating (5-aza) and methylating (budesonide) agents. The level of DNA methylation in the second CpG island of ckα promoter was determined by PCR-based method. 5-aza and budesonide increased the methylation of the selected CpG island compared to untreated control. Treatment with the drugs produced opposite effect, with 5-aza induced ckα promoter activity and gene expression while budesonide suppressed the promoter activity and mRNA level of this gene. Deletion of a region containing the second CpG island on ckα promoter resulted in significantly lower promoter activity. In conclusion, this study showed that DNA methylation could be one of the mechanisms that regulate the expression of ckα gene. Penerbit Universiti Kebangsaan Malaysia 2020-01 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/14747/1/ARTIKEL%2020.pdf Siti Aisyah Faten Mohamed Sa'dom, and Nur Farah Hani Azemi, and Mohammad Shahrizal Mohammad Umar, and Yoke, Hiang Yee and Wei, Cun See Too and Ling, Ling Few (2020) DNA methylation of human choline kinase alpha gene. Sains Malaysiana, 49 (1). pp. 161-168. ISSN 0126-6039 http://www.ukm.my/jsm/malay_journals/jilid49bil1_2020/KandunganJilid49Bil1_2020.html
spellingShingle Siti Aisyah Faten Mohamed Sa'dom,
Nur Farah Hani Azemi,
Mohammad Shahrizal Mohammad Umar,
Yoke, Hiang Yee
Wei, Cun See Too
Ling, Ling Few
DNA methylation of human choline kinase alpha gene
title DNA methylation of human choline kinase alpha gene
title_full DNA methylation of human choline kinase alpha gene
title_fullStr DNA methylation of human choline kinase alpha gene
title_full_unstemmed DNA methylation of human choline kinase alpha gene
title_short DNA methylation of human choline kinase alpha gene
title_sort dna methylation of human choline kinase alpha gene
url http://journalarticle.ukm.my/14747/1/ARTIKEL%2020.pdf
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