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    Disrupted miRNA Biogenesis Machinery Reveals Common Molecular Pathways and Diagnostic Potential in MDS and AML
    (Mdpi, 2025) Cevik, Kenan; Ay, Mustafa Ertan; Tombak, Anil; Ay, Ozlem Izci; Karakas, Umit; Erdal, Mehmet Emin
    Background: 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.
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    Effects of electromagnetic radiation on neurogenesis and gene expression in amniocytes
    (Taylor & Francis Ltd, 2023) Uzun, Cosar; Erdal, Nurten; Ay, Ozlem Izci; Karakas, Umit; Yildirim, Didem Derici; Durukan, Huseyin; Akdag, Mahmut Berat
    The aim of the study was to investigate the genetic effects of commonly used radiofrequency on the amniocytes of pregnant women by examining the changes in the expression of genes related to signal transduction and neurogenesis induced by electromagnetic fields of radiofrequencies of 1800 and 2100 MHz by real-time PCR. Upon exposure of the amniocytes to electromagnetic radiation of 2100 MHz at high field strength, the expression levels of genes with important functions in the Wnt signaling pathways as well as neurogenesis-related genes were increased. The findings suggest that radiofrequency at high field strengths can have genotoxic effects during pregnancy.
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    Short-Term Effects of Extremely Low-Frequency Electromagnetic Fields on Neurogenesis and Wnt Signaling in Amniotic Fluid Cells
    (Necmettin Erbakan Univ, Fac Medicine-Neu Press, 2025) Uzun, Cosar; Karakas, Umit; Ay, Mustafa Ertan; Ay, Ozlem Izci; Yildiri, Didem Derici; Erdal, Nurten; Erdal, Mehmet Emin
    Background: Extremely low-frequency electromagnetic fields (ELF-EMF) at 50 Hz are prevalent in household electrical systems. Although various studies have examined the effects of ELF-EMF on cell proliferation and gene expression, its impact on amniotic fluid cells (AFCs) remains unclear. Objectives: This study aimed to assess the potential effects of ELF-EMFs on gene expression related to neurogenesis and the Wnt signaling pathway in AFCs. Methods: AFCs were isolated from amniotic fluid obtained via amniocentesis and divided into five groups: control, sham, and three groups exposed to different ELF-EMF intensities (1 mT, 2 mT, 3 mT for 30 minutes/day for 7 days). Expression levels of genes involved in neurogenesis (HES1, Neurog1, Neurog2, Neurod1) and Wnt signaling (SFRP2, SFRP4, SFRP5, APC1) were analyzed using real-time PCR. Results: ELF-EMF exposure did not result in significant changes in gene expression among the experimental groups compared to controls. Conclusion: Short-term exposure (Acute exposure) to ELF-EMF at moderate intensities does not significantly impact gene expression related to neurogenesis or Wnt signaling in AFCs. Future studies should explore prolonged exposure (chronic exposure) and a broader range of intensities to evaluate developmental impacts more comprehensively.