Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as ...Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.展开更多
目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移...目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移及治疗抵抗性中发挥重要作用,并可作为潜在的治疗靶点和生物预测因子。不同的miR-200家族成员及其差异表达介导不同的靶向作用,这可能与信号通路及细胞环境差异有关。结论miR-200家族在TNBC的发生和发展过程中具有关键性的调控作用,这有望为TNBC的治疗及预后评估提供新思路,但其作用机制仍待进一步的深入研究。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82372277(to ZW),82272361(to XS),82271395(to GL)Guangdong Province Basic and Applied Basic Research Fund Project,No.2024A1515010615(to XS)+1 种基金Guangdong Province Natural Youth Promotion Project,No.2314070000241(to GL)Guangzhou Science and Technology Project,No.2025A04J4740(to GL).
文摘Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.
文摘目的总结microRNA-200(miR-200)家族在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的研究进展。方法系统检索并阅读国内外的相关文献,对近年来miR-200家族在TNBC中的研究进展进行综述。结果miR-200家族在TNBC的增殖、侵袭转移及治疗抵抗性中发挥重要作用,并可作为潜在的治疗靶点和生物预测因子。不同的miR-200家族成员及其差异表达介导不同的靶向作用,这可能与信号通路及细胞环境差异有关。结论miR-200家族在TNBC的发生和发展过程中具有关键性的调控作用,这有望为TNBC的治疗及预后评估提供新思路,但其作用机制仍待进一步的深入研究。
