MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression

The growth hormone (GH)–insulin-like growth factor-1 (IGF1) endocrine axis is a central player in normal growth and metabolism as well as in a number of pathologies, including cancer. The GH–IGF1 hormonal system, in addition, has emerged as a major determinant of lifespan and healthspan. Laron syndr...

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Autores principales:	Danielle Yaron-Saminsky, Karthik Nagaraj, Rive Sarfstein, Zvi Laron, Metsada Pasmanik-Chor, Haim Werner
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNA-132-3p insulin-like growth factor-1 (IGF1) Laron syndrome congenital IGF1 deficiency longevity SIRT1 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/eeb9cb2ea6f449418f83d63753f81694
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spelling	oai:doaj.org-article:eeb9cb2ea6f449418f83d63753f816942021-11-11T17:17:08ZMicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression10.3390/ijms2221118611422-00671661-6596https://doaj.org/article/eeb9cb2ea6f449418f83d63753f816942021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11861https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The growth hormone (GH)–insulin-like growth factor-1 (IGF1) endocrine axis is a central player in normal growth and metabolism as well as in a number of pathologies, including cancer. The GH–IGF1 hormonal system, in addition, has emerged as a major determinant of lifespan and healthspan. Laron syndrome (LS), the best characterized entity under the spectrum of the congenital IGF1 deficiencies, results from mutation of the GH receptor (GHR) gene, leading to dwarfism, obesity and other defects. Consistent with the key role of IGF1 in cellular proliferation, epidemiological studies have shown that LS patients are protected from cancer development. While reduced expression of components of the GH-IGF1 axis is associated with enhanced longevity in animal models, it is still unknown whether LS is associated with an increased lifespan. MicroRNAs (miRs) are endogenous short non-coding RNAs that regulate the expression of complementary mRNAs. While a number of miRs involved in the regulation of IGF components have been identified, no previous studies have investigated the differential expression of miRs in congenital IGF1 deficiencies. The present study was aimed at identifying miRs that are differentially expressed in LS and that might account for the phenotypic features of LS patients, including longevity. Our genomic analyses provide evidence that miR-132-3p was highly expressed in LS. In addition, we identified SIRT1, a member of the sirtuin family of histone deacetylases, as a target for negative regulation by miR-132-3p. The data was consistent with the notion that low concentrations of IGF1 in LS lead to elevated miR-132-3p levels, with ensuing reduction in SIRT1 gene expression. The impact of the IGF1-miR-132-3p-SIRT1 loop on aging merits further investigation.Danielle Yaron-SaminskyKarthik NagarajRive SarfsteinZvi LaronMetsada Pasmanik-ChorHaim WernerMDPI AGarticlemicroRNA-132-3pinsulin-like growth factor-1 (IGF1)Laron syndromecongenital IGF1 deficiencylongevitySIRT1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11861, p 11861 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA-132-3p insulin-like growth factor-1 (IGF1) Laron syndrome congenital IGF1 deficiency longevity SIRT1 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	microRNA-132-3p insulin-like growth factor-1 (IGF1) Laron syndrome congenital IGF1 deficiency longevity SIRT1 Biology (General) QH301-705.5 Chemistry QD1-999 Danielle Yaron-Saminsky Karthik Nagaraj Rive Sarfstein Zvi Laron Metsada Pasmanik-Chor Haim Werner MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
description	The growth hormone (GH)–insulin-like growth factor-1 (IGF1) endocrine axis is a central player in normal growth and metabolism as well as in a number of pathologies, including cancer. The GH–IGF1 hormonal system, in addition, has emerged as a major determinant of lifespan and healthspan. Laron syndrome (LS), the best characterized entity under the spectrum of the congenital IGF1 deficiencies, results from mutation of the GH receptor (GHR) gene, leading to dwarfism, obesity and other defects. Consistent with the key role of IGF1 in cellular proliferation, epidemiological studies have shown that LS patients are protected from cancer development. While reduced expression of components of the GH-IGF1 axis is associated with enhanced longevity in animal models, it is still unknown whether LS is associated with an increased lifespan. MicroRNAs (miRs) are endogenous short non-coding RNAs that regulate the expression of complementary mRNAs. While a number of miRs involved in the regulation of IGF components have been identified, no previous studies have investigated the differential expression of miRs in congenital IGF1 deficiencies. The present study was aimed at identifying miRs that are differentially expressed in LS and that might account for the phenotypic features of LS patients, including longevity. Our genomic analyses provide evidence that miR-132-3p was highly expressed in LS. In addition, we identified SIRT1, a member of the sirtuin family of histone deacetylases, as a target for negative regulation by miR-132-3p. The data was consistent with the notion that low concentrations of IGF1 in LS lead to elevated miR-132-3p levels, with ensuing reduction in SIRT1 gene expression. The impact of the IGF1-miR-132-3p-SIRT1 loop on aging merits further investigation.
format	article
author	Danielle Yaron-Saminsky Karthik Nagaraj Rive Sarfstein Zvi Laron Metsada Pasmanik-Chor Haim Werner
author_facet	Danielle Yaron-Saminsky Karthik Nagaraj Rive Sarfstein Zvi Laron Metsada Pasmanik-Chor Haim Werner
author_sort	Danielle Yaron-Saminsky
title	MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
title_short	MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
title_full	MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
title_fullStr	MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
title_full_unstemmed	MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression
title_sort	microrna 132-3p is upregulated in laron syndrome patients and controls longevity gene expression
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/eeb9cb2ea6f449418f83d63753f81694
work_keys_str_mv	AT danielleyaronsaminsky microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression AT karthiknagaraj microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression AT rivesarfstein microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression AT zvilaron microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression AT metsadapasmanikchor microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression AT haimwerner microrna1323pisupregulatedinlaronsyndromepatientsandcontrolslongevitygeneexpression
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MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression

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