Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma

Abstract Adenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, A...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bokyung Ahn, Yang Seok Chae, Soo Kyung Lee, Moa Kim, Hyeon Soo Kim, Ji Wook Moon, Sun-Hwa Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8f0022518e1c4528b9cb5d4ec0eaba7c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8f0022518e1c4528b9cb5d4ec0eaba7c
record_format	dspace
spelling	oai:doaj.org-article:8f0022518e1c4528b9cb5d4ec0eaba7c2021-12-02T17:22:57ZIdentification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma10.1038/s41598-021-92147-62045-2322https://doaj.org/article/8f0022518e1c4528b9cb5d4ec0eaba7c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92147-6https://doaj.org/toc/2045-2322Abstract Adenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, AK5 was significantly hypermethylated in CRC compared to adjacent normal tissues (P < 0.0001) and normal tissues (P = 0.0015). Although the difference in mRNA expression was not statistically significant in all of them, the selected 49 cases of CRC tissues with AK5 hypermethylation with the cut off value of 40% showed a significant inverse correlation with mRNA expression (P = 0.0003). DNA methylation of AK5 promoter significantly decreased and AK5 expression recovered by 5-aza-2′-deoxycytidine, DNA methyltransferase inhibitor in CRC cell lines. In addition, AK5 promoter activity significantly decreased due to DNA methyltransferase, and it increased due to 5-aza. Moreover, AK5 regulated the phosphorylated AMPK and mTOR phosphorylation and inhibited the cell migration and cell invasion in CRC cell lines. Furthermore, low AK5 expression is associated with poor differentiation (P = 0.014). These results demonstrate that the AK5 promoter is frequently hypermethylated and induced methylation-mediated gene down-regulation. AK5 expression regulates AMPK/mTOR signalling and may be closely related to metastasis in colorectal adenocarcinoma.Bokyung AhnYang Seok ChaeSoo Kyung LeeMoa KimHyeon Soo KimJi Wook MoonSun-Hwa ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bokyung Ahn Yang Seok Chae Soo Kyung Lee Moa Kim Hyeon Soo Kim Ji Wook Moon Sun-Hwa Park Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
description	Abstract Adenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, AK5 was significantly hypermethylated in CRC compared to adjacent normal tissues (P < 0.0001) and normal tissues (P = 0.0015). Although the difference in mRNA expression was not statistically significant in all of them, the selected 49 cases of CRC tissues with AK5 hypermethylation with the cut off value of 40% showed a significant inverse correlation with mRNA expression (P = 0.0003). DNA methylation of AK5 promoter significantly decreased and AK5 expression recovered by 5-aza-2′-deoxycytidine, DNA methyltransferase inhibitor in CRC cell lines. In addition, AK5 promoter activity significantly decreased due to DNA methyltransferase, and it increased due to 5-aza. Moreover, AK5 regulated the phosphorylated AMPK and mTOR phosphorylation and inhibited the cell migration and cell invasion in CRC cell lines. Furthermore, low AK5 expression is associated with poor differentiation (P = 0.014). These results demonstrate that the AK5 promoter is frequently hypermethylated and induced methylation-mediated gene down-regulation. AK5 expression regulates AMPK/mTOR signalling and may be closely related to metastasis in colorectal adenocarcinoma.
format	article
author	Bokyung Ahn Yang Seok Chae Soo Kyung Lee Moa Kim Hyeon Soo Kim Ji Wook Moon Sun-Hwa Park
author_facet	Bokyung Ahn Yang Seok Chae Soo Kyung Lee Moa Kim Hyeon Soo Kim Ji Wook Moon Sun-Hwa Park
author_sort	Bokyung Ahn
title	Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
title_short	Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
title_full	Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
title_fullStr	Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
title_full_unstemmed	Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
title_sort	identification of novel dna hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8f0022518e1c4528b9cb5d4ec0eaba7c
work_keys_str_mv	AT bokyungahn identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT yangseokchae identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT sookyunglee identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT moakim identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT hyeonsookim identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT jiwookmoon identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma AT sunhwapark identificationofnoveldnahypermethylationoftheadenylatekinase5promoterincolorectaladenocarcinoma
_version_	1718380983099588608

Identification of novel DNA hypermethylation of the adenylate kinase 5 promoter in colorectal adenocarcinoma

Ejemplares similares