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Cagnan, Ilgin; Keles, Mustafa; Keskus, Ayse Gokce; Tombaz, Melike; Sahan, Ozge Burcu; Aerts-Kaya, Fatima; Uckan-Cetinkaya, Duygu; Konu, Ozlen; Gunel-Ozcan, Aysen
{ "DOI": "10.1007/s13577-021-00626-9", "abstract": "Fanconi anemia (FA) is a rare genetic disorder characterized by genomic instability, developmental defects, and bone marrow (BM) failure. Hematopoietic stem cells (HSCs) in BM interact with the mesenchymal stem/stromal cells (MSCs); and this partly sustains the tissue homeostasis. MicroRNAs (miRNAs) can play a critical role during these interactions possibly via paracrine mechanisms. This is the first study addressing the miRNA profile of FA BM-MSCs obtained before and after BM transplantation (preBMT and postBMT, respectively). Non-coding RNA expression profiling and quality control analyses were performed in Donors (n = 13), FA preBMT (n = 11), and FA postBMT (n = 6) BM-MSCs using GeneChip miRNA 2.0 Array. Six Donor-FA preBMT pairs were used to identify a differentially expressed miRNA expression signature containing 50 miRNAs, which exhibited a strong correlation with the signature obtained from unpaired samples. Five miRNAs (hsa-miR-146a-5p, hsa-miR-148b-3p, hsa-miR-187-3p, hsa-miR-196b-5p, and hsa-miR-25-3p) significantly downregulated in both the paired and unpaired analyses were used to generate the BM-MSCs' miRNA-BM mononuclear mRNA networks upon integration of a public dataset (GSE16334; studying Donor versus FA samples). Functionally enriched KEGG pathways included cellular senescence, miRNAs, and pathways in cancer. Here, we showed that hsa-miR-146a-5p and hsa-miR-874-3p were rescued upon BMT (n = 3 triplets). The decrease in miR-146a-5p was also validated using RT-qPCR and emerged as a strong candidate as a modulator of BM mRNAs in FA patients.", "author": [ { "family": "Cagnan", "given": " Ilgin" }, { "family": "Keles", "given": " Mustafa" }, { "family": "Keskus", "given": " Ayse Gokce" }, { "family": "Tombaz", "given": " Melike" }, { "family": "Sahan", "given": " Ozge Burcu" }, { "family": "Aerts-Kaya", "given": " Fatima" }, { "family": "Uckan-Cetinkaya", "given": " Duygu" }, { "family": "Konu", "given": " Ozlen" }, { "family": "Gunel-Ozcan", "given": " Aysen" } ], "container_title": "HUMAN CELL", "id": "238442", "issue": "1", "issued": { "date-parts": [ [ 2022, 1, 1 ] ] }, "page": "111-124", "title": "Global miRNA expression of bone marrow mesenchymal stem/stromal cells derived from Fanconi anemia patients", "type": "article-journal", "volume": "35" }
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