Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting

Cancer cells are able to proliferate in an unregulated manner. There are several mechanisms involved that propel such neoplastic transformations. One of these processes involves bypassing cell death through changes in gene expression and, consequently, cell growth. This involves a complex epigenetic...

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Autores principales:	Aisha Farhana, Avin Ee-Hwan Koh, Sangeetha Kothandan, Abdullah Alsrhani, Pooi Ling Mok, Suresh Kumar Subbiah
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	camptothecin colorectal cancer <i>Wnt</i> signaling pathway bioinformatics natural product Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/25ec632734af4299a4737134e6bf91ef
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spelling	oai:doaj.org-article:25ec632734af4299a4737134e6bf91ef2021-11-25T17:55:02ZTreatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting10.3390/ijms2222122861422-00671661-6596https://doaj.org/article/25ec632734af4299a4737134e6bf91ef2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12286https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Cancer cells are able to proliferate in an unregulated manner. There are several mechanisms involved that propel such neoplastic transformations. One of these processes involves bypassing cell death through changes in gene expression and, consequently, cell growth. This involves a complex epigenetic interaction within the cell, which drives it towards oncogenic transformations. These epigenetic events augment cellular growth by potentially altering chromatin structures and influencing key gene expressions. Therapeutic mechanisms have been developed to combat this by taking advantage of the underlying oncogenic mechanisms through chemical modulation. Camptothecin (CPT) is an example of this type of drug. It is a selective topoisomerase I inhibitor that is effective against many cancers, such as colorectal cancer. Previously, we successfully formulated a magnetic nanocarrier-conjugated CPT with β-cyclodextrin and iron NPs (Fe<sub>3</sub>O<sub>4</sub>) cross-linked using EDTA (CPT-CEF). Compared to CPT alone, it boasts higher efficacy due to its selective targeting and increased solubility. In this study, we treated HT29 colon cancer cells with CPT-CEF and attempted to investigate the cytotoxic effects of the formulation through an epigenetic perspective. By using RNA-Seq, several differentially expressed genes were obtained (<i>p</i> < 0.05). Enrichr was then used for the over-representation analysis, and the genes were compared to the epigenetic roadmap and histone modification database. The results showed that the DEGs had a high correlation with epigenetic modifications involving histone H3 acetylation. Furthermore, a subset of these genes was shown to be associated with the <i>Wnt/β-catenin</i> signaling pathway, which is highly upregulated in a large number of cancer cells. These genes could be investigated as downstream therapeutic targets against the uncontrolled proliferation of cancer cells. Further interaction analysis of the identified genes with the key genes of the <i>Wnt/β-catenin</i> signaling pathway in colorectal cancer identified the direct interactors and a few transcription regulators. Further analysis in cBioPortal confirmed their genetic alterations and their distribution across patient samples. Thus, the findings of this study reveal that colorectal cancer could be reversed by treatment with the CPT-CEF nanoparticle-conjugated nanocarrier through an epigenetic mechanism.Aisha FarhanaAvin Ee-Hwan KohSangeetha KothandanAbdullah AlsrhaniPooi Ling MokSuresh Kumar SubbiahMDPI AGarticlecamptothecincolorectal cancer<i>Wnt</i> signaling pathwaybioinformaticsnatural productBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12286, p 12286 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	camptothecin colorectal cancer <i>Wnt</i> signaling pathway bioinformatics natural product Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	camptothecin colorectal cancer <i>Wnt</i> signaling pathway bioinformatics natural product Biology (General) QH301-705.5 Chemistry QD1-999 Aisha Farhana Avin Ee-Hwan Koh Sangeetha Kothandan Abdullah Alsrhani Pooi Ling Mok Suresh Kumar Subbiah Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
description	Cancer cells are able to proliferate in an unregulated manner. There are several mechanisms involved that propel such neoplastic transformations. One of these processes involves bypassing cell death through changes in gene expression and, consequently, cell growth. This involves a complex epigenetic interaction within the cell, which drives it towards oncogenic transformations. These epigenetic events augment cellular growth by potentially altering chromatin structures and influencing key gene expressions. Therapeutic mechanisms have been developed to combat this by taking advantage of the underlying oncogenic mechanisms through chemical modulation. Camptothecin (CPT) is an example of this type of drug. It is a selective topoisomerase I inhibitor that is effective against many cancers, such as colorectal cancer. Previously, we successfully formulated a magnetic nanocarrier-conjugated CPT with β-cyclodextrin and iron NPs (Fe<sub>3</sub>O<sub>4</sub>) cross-linked using EDTA (CPT-CEF). Compared to CPT alone, it boasts higher efficacy due to its selective targeting and increased solubility. In this study, we treated HT29 colon cancer cells with CPT-CEF and attempted to investigate the cytotoxic effects of the formulation through an epigenetic perspective. By using RNA-Seq, several differentially expressed genes were obtained (<i>p</i> < 0.05). Enrichr was then used for the over-representation analysis, and the genes were compared to the epigenetic roadmap and histone modification database. The results showed that the DEGs had a high correlation with epigenetic modifications involving histone H3 acetylation. Furthermore, a subset of these genes was shown to be associated with the <i>Wnt/β-catenin</i> signaling pathway, which is highly upregulated in a large number of cancer cells. These genes could be investigated as downstream therapeutic targets against the uncontrolled proliferation of cancer cells. Further interaction analysis of the identified genes with the key genes of the <i>Wnt/β-catenin</i> signaling pathway in colorectal cancer identified the direct interactors and a few transcription regulators. Further analysis in cBioPortal confirmed their genetic alterations and their distribution across patient samples. Thus, the findings of this study reveal that colorectal cancer could be reversed by treatment with the CPT-CEF nanoparticle-conjugated nanocarrier through an epigenetic mechanism.
format	article
author	Aisha Farhana Avin Ee-Hwan Koh Sangeetha Kothandan Abdullah Alsrhani Pooi Ling Mok Suresh Kumar Subbiah
author_facet	Aisha Farhana Avin Ee-Hwan Koh Sangeetha Kothandan Abdullah Alsrhani Pooi Ling Mok Suresh Kumar Subbiah
author_sort	Aisha Farhana
title	Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
title_short	Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
title_full	Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
title_fullStr	Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
title_full_unstemmed	Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting
title_sort	treatment of ht29 human colorectal cancer cell line with nanocarrier-encapsulated camptothecin reveals histone modifier genes in the <i>wnt</i> signaling pathway as important molecular cues for colon cancer targeting
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/25ec632734af4299a4737134e6bf91ef
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Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the <i>Wnt</i> Signaling Pathway as Important Molecular Cues for Colon Cancer Targeting

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