Disrupted miRNA Biogenesis Machinery Reveals Common Molecular Pathways and Diagnostic Potential in MDS and AML

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dc.authorid0000-0003-2108-1316
dc.authorid0000-0002-7195-1845
dc.authorid0000-0002-6191-2930
dc.authorid0000-0002-4847-6943
dc.authorid0000-0001-9321-5876
dc.authorid0009-0002-5330-8554
dc.contributor.authorCevik, Kenan
dc.contributor.authorAy, Mustafa Ertan
dc.contributor.authorTombak, Anil
dc.contributor.authorAy, Ozlem Izci
dc.contributor.authorKarakas, Umit
dc.contributor.authorErdal, Mehmet Emin
dc.date.accessioned2026-02-28T12:18:14Z
dc.date.available2026-02-28T12:18:14Z
dc.date.issued2025
dc.departmentBayburt Üniversitesi
dc.description.abstractBackground: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal stem cell disorders in which disrupted post-transcriptional regulation contributes to aberrant hematopoiesis and leukemic transformation. The miRNA biogenesis machinery, which comprises Drosha, DGCR8, Dicer, TARBP2, and AGO1, ensures the precise maturation of miRNAs that control lineage commitment and proliferation. However, the extent to which alterations in this pathway reshape hematopoietic gene networks during myeloid disease evolution remains largely unexplored. Methods: Bone marrow samples from newly diagnosed, untreated MDS and AML patients and matched healthy controls were analyzed for the expression of five key miRNA biogenesis genes using quantitative real-time PCR. Statistical comparisons, correlation matrices, and ROC analyses were performed to characterize gene-expression differences. These results were integrated with multigene logistic modeling, decision-curve analysis, and exploratory random forest/SHAP approaches to evaluate molecular interactions and diagnostic relevance. Results: DROSHA, DICER1, and TARBP2 were significantly downregulated in both MDS and AML, suggesting impaired miRNA maturation and a loss of global post-transcriptional control. DGCR8 expression increased across higher-risk MDS groups, suggesting compensatory activation of the Microprocessor complex, whereas AGO1 levels remained relatively stable, consistent with partial maintenance of RISC function. Correlation analyses revealed a co-regulated DROSHA-TARBP2-AGO1 module. ROC, logistic, and machine learning models identified DGCR8 and DICER1 as the strongest diagnostic discriminators. The integrated five-gene signature achieved high discriminative performance (AUC approximate to 0.98) and showed promise but remains preliminary potential for clinical application. Conclusions: Our findings suggest that defects in miRNA biogenesis disrupt hematopoietic homeostasis, reflecting common mechanisms in MDS and AML. The dysregulation of DICER1, DGCR8, and TARBP2 offers insights into miRNA-driven leukemogenesis and may pave the way for miRNA-based diagnostic and therapeutic strategies, pending validation in larger cohorts. Although transcript-level data are provided, future studies should include functional validation to determine the impact on downstream miRNA processing and hematopoietic pathways.
dc.description.sponsorshipMersin University Scientific Research Projects Coordination Unit [2015-TP3-1205]
dc.description.sponsorshipThis study is supported by Mersin University Scientific Research Projects Coordination Unit. (Project Number: 2015-TP3-1205).
dc.identifier.doi10.3390/biomedicines13123082
dc.identifier.issn2227-9059
dc.identifier.issue12
dc.identifier.pmid41463093
dc.identifier.scopus2-s2.0-105025937853
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/biomedicines13123082
dc.identifier.urihttps://hdl.handle.net/20.500.12403/6180
dc.identifier.volume13
dc.identifier.wosWOS:001646915500001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofBiomedicines
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260218
dc.subjectAML
dc.subjectMDS
dc.subjectmiRNA biogenesis
dc.subjectDROSHA/DICER1 genes dysregulation
dc.subjectprecision diagnostics
dc.titleDisrupted miRNA Biogenesis Machinery Reveals Common Molecular Pathways and Diagnostic Potential in MDS and AML
dc.typeArticle

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