The Mechanism of Oxymatrine Targeting miR-27a-3p/PPAR- Signaling Pathway through m6A Modification to Regulate the Influence on Hemangioma Stem Cells on Propranolol Resistance
Cancers(2023)
摘要
Simple Summary In this study, the researchers aimed to understand the mechanism behind the resistance of hemangioma stem cells (HemSCs) to propranolol, a commonly used drug for hemangioma treatment. They investigated the role of a specific signaling pathway involving miR-27a-3p and PPAR-gamma, as well as the impact of a treatment called oxymatrine (OMT). The findings revealed that miR-27a-3p negatively controlled the peroxisome-proliferator-activated receptor gamma (PPAR-gamma), which contributed to the resistance of HemSCs to propranolol. OMT treatment accelerated the progression and adipocyte differentiation of HemSCs via modulating the miR-27a-3p/PPAR-gamma axis, thus inhibiting their resistance to propranolol. This research sheds light on the potential of OMT as a therapeutic strategy for hemangiomas and highlights the importance of targeting the miR-27a-3p/PPAR-gamma pathway. These findings may have implications for improving the effectiveness of propranolol (PPNL) treatment and advancing the understanding of hemangioma biology in the research community.Abstract Objective: The proliferation and migration of hemangioma stem cells (HemSCs) induced apoptosis and adipose differentiation as well as increased the sensitivity of HemSCs to propranolol (PPNL). MiR-27a-3p negatively controlled the peroxisome-proliferator-activated receptor gamma (PPAR-gamma) level, counteracting the effect of PPAR-gamma on HemSC progression and PPNL resistance. OMT accelerated HemSC progression and adipocyte differentiation via modulating the miR-27a-3p/PPAR-gamma axis, inhibiting HemSC resistance to PPNL. In tumor-forming experiments, OMT exhibited a dose-dependent inhibitory effect on the volume of IH PPNL-resistant tumors, which was partially dependent on the regulation of m6A methylation transfer enzyme METTL3 and the miR-27a-3p/PPAR-gamma axis, thereby inducing apoptosis. Conclusions: We conclude that OMT regulates IH and influences PPNL resistance via targeting the miR-27a-3p/PPAR-gamma signaling pathway through m6A modification.
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关键词
hemangioma,oxymatrine,propranolol,adipose differentiation,drug resistance
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