{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:06Z","timestamp":1760143806322,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ5\/02229","503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"],"award-info":[{"award-number":["2015\/19\/B\/NZ5\/02229","503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ5\/02229","503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"],"award-info":[{"award-number":["2015\/19\/B\/NZ5\/02229","503\/1-090-04\/503-11-003","503\/1-090-04\/503-11-001-19"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u20136 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.<\/jats:p>","DOI":"10.3390\/jcm11123395","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"3395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["mTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in microRNA Serum Profile"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-1033","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Pawlik","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-457X","authenticated-orcid":false,"given":"Urszula","family":"Smyczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, ul. Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-5833","authenticated-orcid":false,"given":"Szymon","family":"Grabia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, ul. Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Fendler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, ul. Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1956-5063","authenticated-orcid":false,"given":"Izabela","family":"Dr\u00f3\u017cd\u017c","sequence":"additional","affiliation":[{"name":"Department of Clinical and Laboratory Genetics, Medical University of Lodz, 92-231 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"B\u0105bol-Pokora","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kotulska","sequence":"additional","affiliation":[{"name":"Department of Neurology & Epileptology and Pediatric Rehabilitation, The Children\u2019s Memorial Health Institute, ul. Dzieci Polskich 20, 00-999 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-6326","authenticated-orcid":false,"given":"Sergiusz","family":"J\u00f3\u017awiak","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Medical University of Warsaw, ul. Banacha 1A, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julita","family":"Borkowska","sequence":"additional","affiliation":[{"name":"Department of Neurology & Epileptology and Pediatric Rehabilitation, The Children\u2019s Memorial Health Institute, ul. Dzieci Polskich 20, 00-999 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-4274","authenticated-orcid":false,"given":"Joanna","family":"Treli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.spen.2015.10.002","article-title":"Genotype\/Phenotype Correlations in Tuberous Sclerosis Complex","volume":"22","author":"Curatolo","year":"2015","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1\u2013TSC2 complex: A molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. 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