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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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11861 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:01:13Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:13Z |
| publishDate | 2021-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-eeb9cb2ea6f449418f83d63753f816942023-11-22T20:59:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122211186110.3390/ijms222111861MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene ExpressionDanielle Yaron-Saminsky0Karthik Nagaraj1Rive Sarfstein2Zvi Laron3Metsada Pasmanik-Chor4Haim Werner5Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelSchneider Children’s Medical Center, Endocrinology and Diabetes Research Unit, 49292 Petah Tikva, IsraelBioinformatics Unit, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, IsraelThe 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.https://www.mdpi.com/1422-0067/22/21/11861microRNA-132-3pinsulin-like growth factor-1 (IGF1)Laron syndromecongenital IGF1 deficiencylongevitySIRT1 |
| spellingShingle | 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 International Journal of Molecular Sciences microRNA-132-3p insulin-like growth factor-1 (IGF1) Laron syndrome congenital IGF1 deficiency longevity SIRT1 |
| title | 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_short | 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 |
| topic | microRNA-132-3p insulin-like growth factor-1 (IGF1) Laron syndrome congenital IGF1 deficiency longevity SIRT1 |
| url | https://www.mdpi.com/1422-0067/22/21/11861 |
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