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mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile
The aim of this study was to determine the serum profiles of miRNAs in patients with tuberous sclerosis (TSC) upon sirolimus treatment and compare them with those previously treated with everolimus in a similarly designed experiment. Serum microRNA profiling was performed in ten TSC patients before...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224825/ https://www.ncbi.nlm.nih.gov/pubmed/35743464 http://dx.doi.org/10.3390/jcm11123395 |
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author | Pawlik, Bartłomiej Smyczyńska, Urszula Grabia, Szymon Fendler, Wojciech Dróżdż, Izabela Bąbol-Pokora, Katarzyna Kotulska, Katarzyna Jóźwiak, Sergiusz Borkowska, Julita Młynarski, Wojciech Trelińska, Joanna |
author_facet | Pawlik, Bartłomiej Smyczyńska, Urszula Grabia, Szymon Fendler, Wojciech Dróżdż, Izabela Bąbol-Pokora, Katarzyna Kotulska, Katarzyna Jóźwiak, Sergiusz Borkowska, Julita Młynarski, Wojciech Trelińska, Joanna |
author_sort | Pawlik, Bartłomiej |
collection | PubMed |
description | The aim of this study was to determine the serum profiles of miRNAs in patients with tuberous sclerosis (TSC) upon sirolimus treatment and compare them with those previously treated with everolimus in a similarly designed experiment. Serum microRNA profiling was performed in ten TSC patients before sirolimus therapy and again after 3–6 months using qPCR panels (Exiqon). Of 752 tested miRNAs, 28 showed significant differences in expression between TSC patients before and after sirolimus treatment. Of these, 11 miRNAs were dysregulated in the same directions as in the sirolimus groupcompared with the previously described everolimus group, miR-142-3p, miR-29c-3p, miR-150-5p, miR-425-5p, miR-376a-3p, miR-376a-3p, miR-532-3p, and miR-136-5p were upregulated, while miR-15b-3p, miR-100-5p, and miR-185-5p were downregulated. The most significant changes of expression, with fold changes exceeding 1.25 for both treatments, were noted for miR-136-5p, miR-376a-3p, and miR-150-5p. The results of a pathway analysis of the possible target genes for these miRNAs indicated the involvement of the Ras and MAPK signaling pathway. Upregulation of miR-136, miR-376a-3p, and miR-150-5p was noted in TSC patients treated with mTOR inhibitors, indicating a role in the downregulation of the mTOR pathway. Further studies are needed to determine the relationship between upregulated microRNAs and treatment efficacy. |
format | Online Article Text |
id | pubmed-9224825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92248252022-06-24 mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile Pawlik, Bartłomiej Smyczyńska, Urszula Grabia, Szymon Fendler, Wojciech Dróżdż, Izabela Bąbol-Pokora, Katarzyna Kotulska, Katarzyna Jóźwiak, Sergiusz Borkowska, Julita Młynarski, Wojciech Trelińska, Joanna J Clin Med Article The aim of this study was to determine the serum profiles of miRNAs in patients with tuberous sclerosis (TSC) upon sirolimus treatment and compare them with those previously treated with everolimus in a similarly designed experiment. Serum microRNA profiling was performed in ten TSC patients before sirolimus therapy and again after 3–6 months using qPCR panels (Exiqon). Of 752 tested miRNAs, 28 showed significant differences in expression between TSC patients before and after sirolimus treatment. Of these, 11 miRNAs were dysregulated in the same directions as in the sirolimus groupcompared with the previously described everolimus group, miR-142-3p, miR-29c-3p, miR-150-5p, miR-425-5p, miR-376a-3p, miR-376a-3p, miR-532-3p, and miR-136-5p were upregulated, while miR-15b-3p, miR-100-5p, and miR-185-5p were downregulated. The most significant changes of expression, with fold changes exceeding 1.25 for both treatments, were noted for miR-136-5p, miR-376a-3p, and miR-150-5p. The results of a pathway analysis of the possible target genes for these miRNAs indicated the involvement of the Ras and MAPK signaling pathway. Upregulation of miR-136, miR-376a-3p, and miR-150-5p was noted in TSC patients treated with mTOR inhibitors, indicating a role in the downregulation of the mTOR pathway. Further studies are needed to determine the relationship between upregulated microRNAs and treatment efficacy. MDPI 2022-06-13 /pmc/articles/PMC9224825/ /pubmed/35743464 http://dx.doi.org/10.3390/jcm11123395 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pawlik, Bartłomiej Smyczyńska, Urszula Grabia, Szymon Fendler, Wojciech Dróżdż, Izabela Bąbol-Pokora, Katarzyna Kotulska, Katarzyna Jóźwiak, Sergiusz Borkowska, Julita Młynarski, Wojciech Trelińska, Joanna mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title | mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title_full | mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title_fullStr | mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title_full_unstemmed | mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title_short | mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile |
title_sort | mtor inhibitor treatment in patients with tuberous sclerosis complex is associated with specific changes in microrna serum profile |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224825/ https://www.ncbi.nlm.nih.gov/pubmed/35743464 http://dx.doi.org/10.3390/jcm11123395 |
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