Seçme, M.Dodurga, Y.Demirkan, N.Ç.Kaçar, N.Günel, N.S.Açıkbaş, İ.2024-08-252024-08-2520240378-1119https://doi.org/10.1016/j.gene.2023.147825https://hdl.handle.net/11454/100574Cutaneous T-cell lymphomas (CTCL) encompass a group of diseases characterized by the presence of malignant clonal CD4+ T lymphocytes in the skin. Mycosis fungoides (MF) is the most prevalent form of CTCL, accounting for approximately 60 % of cutaneous T-cell lymphomas and 50 % of all primary cutaneous lymphomas. Despite ongoing research, the precise pathogenesis of MF remains incompletely understood. Toll-like receptors (TLRs) have the ability to specifically recognize ligands, subsequently induce the expression of diverse genes and activate innate immunity within the cell. Furthermore, miRNAs play a crucial role in regulating various aspects of immune cell function. The aim of our study was to explore the potential roles of TLRs and the genes implicated in their signal transduction, along with the expression status of miRNAs in the mechanisms underlying MF. Additionally, we assessed the clonal status and compared it with clinicopathological data using a T-cell clonality assay. To determine the expression status of TLR pathway genes and miRNAs, we conducted RT-PCR analysis on 52 MF samples and 50 control paraffin block materials. Pathway analysis were conducted using the KEGG database. T-cell receptor (TCR) gamma clonality changes were evaluated. Results from the study revealed increased expressions of TLR-1, -4, -8, IRF7, TRAF3, MEK1, MEK2, Elk1, NFkB, hsa-miR-21-5p, and hsa-miR-155-5p, as well as decreased expressions of hsa-miR-130a-3p, hsa-miR-210-3p, and hsa-let-7e-5p in the MF group. TCR gamma clonal change analysis demonstrated that 55.5 % of the analysed DNAs exhibited monoclonal and biallelic patterns, while 45.5 % displayed polyclonality. These findings collectively suggest the potential influence and therapeutic possibilities of the TLR signalling pathway in the molecular pathogenesis of MF. © 2023 Elsevier B.V.en10.1016/j.gene.2023.147825info:eu-repo/semantics/closedAccessClonalitymiRNAsMycosis fungoidesToll-like receptorsDNAimmunoglobulin enhancer binding proteininterferon regulatory factor 7microRNAmicroRNA 130a 3pmicroRNA 146a 5pmicroRNA 155microRNA 155 5pmicroRNA 200a 3pmicroRNA 204 5pmicroRNA 21microRNA 21 5pmicroRNA 210 3pmicroRNA 214 3pmicroRNA 223 3pmicroRNA 224 5pmicroRNA 375microRNA 424 5pmicroRNA let 7e 5pmitogen activated protein kinase kinase 1mitogen activated protein kinase kinase 2paraffintoll like receptortoll like receptor 1toll like receptor 4toll like receptor 8transcription factor Elk 1tumor necrosis factor receptor associated factor 3unclassified drugadolescentadultagedalleleArticlechildclonal variationcontrolled studyDNA determinationElk1 geneERK1 geneERK2 genefemalegene expressiongene functionhistopathologyhumanhuman cellhuman tissueinfantIRAK 4 geneIRAK1 geneIRF 7 geneKEGGmajor clinical studymaleMEK1 geneMEK2 genemolecular pathologymycosis fungoidesMyD88 geneNfkappaB genepathway analysisprotein expressionprotein functionreal time polymerase chain reactionsignal transductionT lymphocyteTAB2 geneTIRAP geneTLR 1 geneTLR 10 geneTLR 2 geneTLR 3 geneTLR 4 geneTLR 5 geneTLR 6 geneTLR 7 geneTLR 8 geneTLR 9 geneTLR geneTLR signalingTRAF 3 geneTRAF 6 geneTRIF genevery elderlyArticle8912-s2.0-8517268186237748629Q2