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Background: Non-coding RNAs (ncRNAs) play crucial roles in regulating hematopoietic and mesenchymal stem cells skewing towards regenerative or modulating commitment. There is gap in understanding how ncRNAs regulate diverse pathways that offer new opportunities for therapeutic targeting in regenerative medicine and disease management.
Methods: The current review examines the dual regulatory mechanisms of ncRNAs in stem cell biology, analyzing their roles as positive (upscale) and negative (downscale) cellular modulators through comprehensive review of ncRNA signaling pathways.
Results: As positive regulators, ncRNAs promote cell survival, regulate the cell cycle, enhance differentiation, selfrenewal, delay senescence, and modulate autophagy to maintain stem cell function. As negative regulators, ncRNAs induce various forms of cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis, often through interactions with long ncRNAs. Additionally, ncRNAs modulate inflammatory responses by influencing proinflammatory cytokines and reducing cell adhesion, further impacting stem cell survival. ncRNAs also influence intercellular communication and signaling pathways, enhancing or suppressing cellular crosstalk essential for stem cell differentiation.
Conclusions: Therefore, ncRNAs demonstrate complex dual regulatory functions in stem cell biology, serving both as protective and detrimental influencers/modulators depending on cellular context. Future research should focus on elucidating ncRNA signaling networks and developing ncRNA-based interventions for stem cell dysfunction and associated pathologies.
DOI: 10.7754/Clin.Lab.2025.250763
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