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

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Cagnan I., Keles M., Keskus A. G., Tombaz M., ŞAHAN Ö. B., AERTS KAYA F. S. F., ...More

HUMAN CELL, vol.35, no.1, pp.111-124, 2022 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1007/s13577-021-00626-9
  • Journal Name: HUMAN CELL
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.111-124
  • Keywords: Fanconi anemia, Bone marrow, Mesenchymal stem, stromal cells, miRNA, Non-coding RNAs, NF-KAPPA-B, STEM-CELLS, EXTRACELLULAR VESICLES, IN-VITRO, PROLIFERATION, FANCD2, DIFFERENTIATION, CONTRIBUTES, PROGENITORS, DYSFUNCTION
  • Open Archive Collection: AVESIS Open Access Collection
  • Hacettepe University Affiliated: Yes

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.