Landscape Of HOXA Genes Methylation in Colorectal Cancer

Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated...

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Main Authors: Muhiddin Ishak, Rashidah Baharudin, Loh Teng-Hern Tan, Learn-Han Lee, Nurul-Syakima Ab Mutalib
Format: Article
Language:English
Published: HH Publisher 2020-05-01
Series:Progress in Microbes and Molecular Biology
Online Access:https://journals.hh-publisher.com/index.php/pmmb/article/view/300
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author Muhiddin Ishak
Rashidah Baharudin
Loh Teng-Hern Tan
Learn-Han Lee
Nurul-Syakima Ab Mutalib
author_facet Muhiddin Ishak
Rashidah Baharudin
Loh Teng-Hern Tan
Learn-Han Lee
Nurul-Syakima Ab Mutalib
author_sort Muhiddin Ishak
collection DOAJ
description Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated HOXA expression influences various aspects of carcinogenesis processes. Therefore, this study aims to elucidate the methylation landscape of HOXA genes in CRC. Twelve pairs of CRC — adjacent normal tissues were subjected to Infinium DNA MethyEPIC array. Differentially methylated regions were identified using the ChAMP Bioconductor and methylation levels of HOXA genes were manually curated. We identified 100 significantly differentially methylated probes annotated to HOXA genes. HOXA3 has the highest number of differentially methylated probes (n=27), followed by HOXA2 (n=20) and HOXA4 (n=14). The majority (43%) of the probes were located at the transcription start site (TSS) 200, which is one of the gene promoters. In respect to CpG islands (CGI), the probes were equally located in the island and shore regions (47% each) while a minor percentage was in the shelf (6%). Our work gave a comprehensive assessment of the DNA methylation pattern of HOXA genes and provide the first evidence of HOXA2, HOXA3 and HOXA4 differential methylation in Malaysian CRC. The new knowledge from this study can be utilized to further increase our understanding of CRC methylomics, particularly on the homeobox A genes. The prognostic and diagnostic roles of the differentially methylated HOXA genes warrant future investigations.
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spelling doaj-art-c51221c13a444f3eb5734172dba268892025-02-04T08:37:05ZengHH PublisherProgress in Microbes and Molecular Biology2637-10492020-05-013110.36877/pmmb.a0000085Landscape Of HOXA Genes Methylation in Colorectal CancerMuhiddin IshakRashidah BaharudinLoh Teng-Hern TanLearn-Han LeeNurul-Syakima Ab Mutalib Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated HOXA expression influences various aspects of carcinogenesis processes. Therefore, this study aims to elucidate the methylation landscape of HOXA genes in CRC. Twelve pairs of CRC — adjacent normal tissues were subjected to Infinium DNA MethyEPIC array. Differentially methylated regions were identified using the ChAMP Bioconductor and methylation levels of HOXA genes were manually curated. We identified 100 significantly differentially methylated probes annotated to HOXA genes. HOXA3 has the highest number of differentially methylated probes (n=27), followed by HOXA2 (n=20) and HOXA4 (n=14). The majority (43%) of the probes were located at the transcription start site (TSS) 200, which is one of the gene promoters. In respect to CpG islands (CGI), the probes were equally located in the island and shore regions (47% each) while a minor percentage was in the shelf (6%). Our work gave a comprehensive assessment of the DNA methylation pattern of HOXA genes and provide the first evidence of HOXA2, HOXA3 and HOXA4 differential methylation in Malaysian CRC. The new knowledge from this study can be utilized to further increase our understanding of CRC methylomics, particularly on the homeobox A genes. The prognostic and diagnostic roles of the differentially methylated HOXA genes warrant future investigations. https://journals.hh-publisher.com/index.php/pmmb/article/view/300
spellingShingle Muhiddin Ishak
Rashidah Baharudin
Loh Teng-Hern Tan
Learn-Han Lee
Nurul-Syakima Ab Mutalib
Landscape Of HOXA Genes Methylation in Colorectal Cancer
Progress in Microbes and Molecular Biology
title Landscape Of HOXA Genes Methylation in Colorectal Cancer
title_full Landscape Of HOXA Genes Methylation in Colorectal Cancer
title_fullStr Landscape Of HOXA Genes Methylation in Colorectal Cancer
title_full_unstemmed Landscape Of HOXA Genes Methylation in Colorectal Cancer
title_short Landscape Of HOXA Genes Methylation in Colorectal Cancer
title_sort landscape of hoxa genes methylation in colorectal cancer
url https://journals.hh-publisher.com/index.php/pmmb/article/view/300
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AT rashidahbaharudin landscapeofhoxagenesmethylationincolorectalcancer
AT lohtengherntan landscapeofhoxagenesmethylationincolorectalcancer
AT learnhanlee landscapeofhoxagenesmethylationincolorectalcancer
AT nurulsyakimaabmutalib landscapeofhoxagenesmethylationincolorectalcancer