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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...

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Autores principales: Pawlik, Bartłomiej, Smyczyńska, Urszula, Grabia, Szymon, Fendler, Wojciech, Dróżdż, Izabela, Bąbol-Pokora, Katarzyna, Kotulska, Katarzyna, Jóźwiak, Sergiusz, Borkowska, Julita, Młynarski, Wojciech, Trelińska, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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