文章：

氧化苦参碱通过m6A修饰靶向miR-27a-3p/PPAR-γ信号通路调控血管瘤干细胞对普萘洛尔耐药性的影响机制

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

原文发布日期：30 October 2023

DOI: 10.3390/cancers15215213

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

目的：氧化苦参碱（OMT）通过诱导血管瘤干细胞（HemSCs）凋亡和脂肪分化，并增强其对普萘洛尔（PPNL）的敏感性，从而抑制婴幼儿血管瘤（IH）的进展。MiR-27a-3p负向调控过氧化物酶体增殖物激活受体γ（PPAR-γ）水平，抵消了PPAR-γ对HemSC进展和PPNL耐药性的影响。OMT通过调控miR-27a-3p/PPAR-γ轴，促进HemSC的凋亡和脂肪细胞分化，抑制HemSC对PPNL的耐药性。在成瘤实验中，OMT对IH PPNL耐药性肿瘤体积表现出剂量依赖性的抑制作用，该作用部分依赖于对m6A甲基转移酶METTL3及miR-27a-3p/PPAR-γ轴的调控，从而诱导细胞凋亡。结论：我们得出结论，OMT通过m6A修饰靶向miR-27a-3p/PPAR-γ信号通路，调控IH并影响其对PPNL的耐药性。

原文链接：

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