The Mechanism of Oxymatrine Targeting miR-27a-3p/PPAR-γ Signaling Pathway through m6A Modification to Regulate the Influence on Hemangioma Stem Cells on Propranolol Resistance

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-γ, 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 γ (PPAR-γ), 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-γ 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-γ 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 γ (PPAR-γ) level, counteracting the effect of PPAR-γ on HemSC progression and PPNL resistance. OMT accelerated HemSC progression and adipocyte differentiation via modulating the miR-27a-3p/PPAR-γ 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-γ axis, thereby inducing apoptosis. Conclusions: We conclude that OMT regulates IH and influences PPNL resistance via targeting the miR-27a-3p/PPAR-γ signaling pathway through m6A modification.