Pawlik Bartłomiej, Smyczyńska Urszula, Grabia Szymon, Fendler Wojciech, Dróżdż Izabela, Bąbol-Pokora Katarzyna, Kotulska Katarzyna, Jóźwiak Sergiusz, Borkowska Julita, Młynarski Wojciech, Trelińska Joanna
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, ul. Sporna 36/50, 91-738 Lodz, Poland.
Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.
J Clin Med. 2022 Jun 13;11(12):3395. doi: 10.3390/jcm11123395.
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.
本研究的目的是确定西罗莫司治疗结节性硬化症（TSC）患者时血清miRNA谱，并在一项设计相似的实验中将其与先前接受依维莫司治疗的患者的血清miRNA谱进行比较。在10例TSC患者接受西罗莫司治疗前及治疗3 - 6个月后，使用qPCR检测板（Exiqon）进行血清微小RNA谱分析。在752个检测的miRNA中，28个在TSC患者西罗莫司治疗前后表达有显著差异。其中，与先前描述的依维莫司组相比，11个miRNA的表达失调方向相同，miR - 142 - 3p、miR - 29c - 3p、miR - 150 - 5p、miR - 425 - 5p、miR - 376a - 3p、miR - 532 - 3p和miR - 136 - 5p上调，而miR - 15b - 3p、miR - 100 - 5p和miR - 185 - 5p下调。两种治疗的表达变化最显著，倍数变化均超过1.25的是miR - 136 - 5p、miR - 376a - 3p和miR - 150 - 5p。对这些miRNA可能的靶基因进行通路分析的结果表明Ras和MAPK信号通路参与其中。在接受mTOR抑制剂治疗的TSC患者中，miR - 136、miR - 376a - 3p和miR - 150 - 5p上调，表明其在mTOR通路下调中起作用。需要进一步研究以确定上调的微小RNA与治疗疗效之间的关系。
