Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers

Abstract MicroRNA is responsible for the fine-tuning of fundamental cellular activities and human disease development. The altered availability of microRNAs, target mRNAs, and other types of endogenous RNAs competing for microRNA interactions reflects the dynamic and conditional property of microRNA...

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Autores principales:	Jiang Shu, Bruno Vieira Resende e Silva, Tian Gao, Zheng Xu, Juan Cui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e9a073a776940c4bdb537dcb27304ca
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spelling	oai:doaj.org-article:5e9a073a776940c4bdb537dcb27304ca2021-12-02T15:05:45ZDynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers10.1038/s41598-017-13470-52045-2322https://doaj.org/article/5e9a073a776940c4bdb537dcb27304ca2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13470-5https://doaj.org/toc/2045-2322Abstract MicroRNA is responsible for the fine-tuning of fundamental cellular activities and human disease development. The altered availability of microRNAs, target mRNAs, and other types of endogenous RNAs competing for microRNA interactions reflects the dynamic and conditional property of microRNA-mediated gene regulation that remains under-investigated. Here we propose a new integrative method to study this dynamic process by considering both competing and cooperative mechanisms and identifying functional modules where different microRNAs co-regulate the same functional process. Specifically, a new pipeline was built based on a meta-Lasso regression model and the proof-of-concept study was performed using a large-scale genomic dataset from ~4,200 patients with 9 cancer types. In the analysis, 10,726 microRNA-mRNA interactions were identified to be associated with a specific stage and/or type of cancer, which demonstrated the dynamic and conditional miRNA regulation during cancer progression. On the other hands, we detected 4,134 regulatory modules that exhibit high fidelity of microRNA function through selective microRNA-mRNA binding and modulation. For example, miR-18a-3p, −320a, −193b-3p, and −92b-3p co-regulate the glycolysis/gluconeogenesis and focal adhesion in cancers of kidney, liver, lung, and uterus. Furthermore, several new insights into dynamic microRNA regulation in cancers have been discovered in this study.Jiang ShuBruno Vieira Resende e SilvaTian GaoZheng XuJuan CuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiang Shu Bruno Vieira Resende e Silva Tian Gao Zheng Xu Juan Cui Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
description	Abstract MicroRNA is responsible for the fine-tuning of fundamental cellular activities and human disease development. The altered availability of microRNAs, target mRNAs, and other types of endogenous RNAs competing for microRNA interactions reflects the dynamic and conditional property of microRNA-mediated gene regulation that remains under-investigated. Here we propose a new integrative method to study this dynamic process by considering both competing and cooperative mechanisms and identifying functional modules where different microRNAs co-regulate the same functional process. Specifically, a new pipeline was built based on a meta-Lasso regression model and the proof-of-concept study was performed using a large-scale genomic dataset from ~4,200 patients with 9 cancer types. In the analysis, 10,726 microRNA-mRNA interactions were identified to be associated with a specific stage and/or type of cancer, which demonstrated the dynamic and conditional miRNA regulation during cancer progression. On the other hands, we detected 4,134 regulatory modules that exhibit high fidelity of microRNA function through selective microRNA-mRNA binding and modulation. For example, miR-18a-3p, −320a, −193b-3p, and −92b-3p co-regulate the glycolysis/gluconeogenesis and focal adhesion in cancers of kidney, liver, lung, and uterus. Furthermore, several new insights into dynamic microRNA regulation in cancers have been discovered in this study.
format	article
author	Jiang Shu Bruno Vieira Resende e Silva Tian Gao Zheng Xu Juan Cui
author_facet	Jiang Shu Bruno Vieira Resende e Silva Tian Gao Zheng Xu Juan Cui
author_sort	Jiang Shu
title	Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
title_short	Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
title_full	Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
title_fullStr	Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
title_full_unstemmed	Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers
title_sort	dynamic and modularized microrna regulation and its implication in human cancers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5e9a073a776940c4bdb537dcb27304ca
work_keys_str_mv	AT jiangshu dynamicandmodularizedmicrornaregulationanditsimplicationinhumancancers AT brunovieiraresendeesilva dynamicandmodularizedmicrornaregulationanditsimplicationinhumancancers AT tiangao dynamicandmodularizedmicrornaregulationanditsimplicationinhumancancers AT zhengxu dynamicandmodularizedmicrornaregulationanditsimplicationinhumancancers AT juancui dynamicandmodularizedmicrornaregulationanditsimplicationinhumancancers
_version_	1718388707326689280

Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers

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