Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer

Abstract Human methyltransferase-like (METTL) proteins transfer methyl groups to nucleic acids, proteins, lipids, and other small molecules, subsequently playing important roles in various cellular processes. In this study, we performed integrated genomic, transcriptomic, proteomic, and clinicopatho...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ion John Campeanu, Yuanyuan Jiang, Lanxin Liu, Maksymilian Pilecki, Alvina Najor, Era Cobani, Morenci Manning, Xiaohong Mary Zhang, Zeng-Quan Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a96f1ed5472a45e0b580b21f83e4bdde
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a96f1ed5472a45e0b580b21f83e4bdde
record_format	dspace
spelling	oai:doaj.org-article:a96f1ed5472a45e0b580b21f83e4bdde2021-12-02T17:55:03ZMulti-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer10.1038/s41598-021-94019-52045-2322https://doaj.org/article/a96f1ed5472a45e0b580b21f83e4bdde2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94019-5https://doaj.org/toc/2045-2322Abstract Human methyltransferase-like (METTL) proteins transfer methyl groups to nucleic acids, proteins, lipids, and other small molecules, subsequently playing important roles in various cellular processes. In this study, we performed integrated genomic, transcriptomic, proteomic, and clinicopathological analyses of 34 METTLs in a large cohort of primary tumor and cell line data. We identified a subset of METTL genes, notably METTL1, METTL7B, and NTMT1, with high frequencies of genomic amplification and/or up-regulation at both the mRNA and protein levels in a spectrum of human cancers. Higher METTL1 expression was associated with high-grade tumors and poor disease prognosis. Loss-of-function analysis in tumor cell lines indicated the biological importance of METTL1, an m7G methyltransferase, in cancer cell growth and survival. Furthermore, functional annotation and pathway analysis of METTL1-associated proteins revealed that, in addition to the METTL1 cofactor WDR4, RNA regulators and DNA packaging complexes may be functionally interconnected with METTL1 in human cancer. Finally, we generated a crystal structure model of the METTL1–WDR4 heterodimeric complex that might aid in understanding the key functional residues. Our results provide new information for further functional study of some METTL alterations in human cancer and might lead to the development of small inhibitors that target cancer-promoting METTLs.Ion John CampeanuYuanyuan JiangLanxin LiuMaksymilian PileckiAlvina NajorEra CobaniMorenci ManningXiaohong Mary ZhangZeng-Quan YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ion John Campeanu Yuanyuan Jiang Lanxin Liu Maksymilian Pilecki Alvina Najor Era Cobani Morenci Manning Xiaohong Mary Zhang Zeng-Quan Yang Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
description	Abstract Human methyltransferase-like (METTL) proteins transfer methyl groups to nucleic acids, proteins, lipids, and other small molecules, subsequently playing important roles in various cellular processes. In this study, we performed integrated genomic, transcriptomic, proteomic, and clinicopathological analyses of 34 METTLs in a large cohort of primary tumor and cell line data. We identified a subset of METTL genes, notably METTL1, METTL7B, and NTMT1, with high frequencies of genomic amplification and/or up-regulation at both the mRNA and protein levels in a spectrum of human cancers. Higher METTL1 expression was associated with high-grade tumors and poor disease prognosis. Loss-of-function analysis in tumor cell lines indicated the biological importance of METTL1, an m7G methyltransferase, in cancer cell growth and survival. Furthermore, functional annotation and pathway analysis of METTL1-associated proteins revealed that, in addition to the METTL1 cofactor WDR4, RNA regulators and DNA packaging complexes may be functionally interconnected with METTL1 in human cancer. Finally, we generated a crystal structure model of the METTL1–WDR4 heterodimeric complex that might aid in understanding the key functional residues. Our results provide new information for further functional study of some METTL alterations in human cancer and might lead to the development of small inhibitors that target cancer-promoting METTLs.
format	article
author	Ion John Campeanu Yuanyuan Jiang Lanxin Liu Maksymilian Pilecki Alvina Najor Era Cobani Morenci Manning Xiaohong Mary Zhang Zeng-Quan Yang
author_facet	Ion John Campeanu Yuanyuan Jiang Lanxin Liu Maksymilian Pilecki Alvina Najor Era Cobani Morenci Manning Xiaohong Mary Zhang Zeng-Quan Yang
author_sort	Ion John Campeanu
title	Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
title_short	Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
title_full	Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
title_fullStr	Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
title_full_unstemmed	Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
title_sort	multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a96f1ed5472a45e0b580b21f83e4bdde
work_keys_str_mv	AT ionjohncampeanu multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT yuanyuanjiang multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT lanxinliu multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT maksymilianpilecki multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT alvinanajor multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT eracobani multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT morencimanning multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT xiaohongmaryzhang multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer AT zengquanyang multiomicsintegrationofmethyltransferaselikeproteinfamilyrevealsclinicaloutcomesandfunctionalsignaturesinhumancancer
_version_	1718379185704009728

Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer

Ejemplares similares