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Global miRNA expression of bone marrow mesenchymal stem/stromal cells derived from Fanconi anemia patients

Cagnan, Ilgin; Keles, Mustafa; Keskus, Ayse Gokce; Tombaz, Melike; Sahan, Ozge Burcu; Aerts-Kaya, Fatima; Uckan-Cetinkaya, Duygu; Konu, Ozlen; Gunel-Ozcan, Aysen


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{
  "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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