Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in I...Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byflow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and verified.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.展开更多
由染色体易位引起的融合基因已成为白血病的主要致病因素。锌指蛋白384(zinc finger protein 384,ZNF384)融合作为急性白血病(acute leukemia,AL)中的非典型融合亚型,在不同的年龄群体中广泛发生。ZNF384具有丰富的融合伴侣,其中E1A结...由染色体易位引起的融合基因已成为白血病的主要致病因素。锌指蛋白384(zinc finger protein 384,ZNF384)融合作为急性白血病(acute leukemia,AL)中的非典型融合亚型,在不同的年龄群体中广泛发生。ZNF384具有丰富的融合伴侣,其中E1A结合蛋白p300(E1A binding protein p300,EP300)、转录因子3(transcription factor 3,TCF3)、TATA-box binding protein associated factor 15(TAF15)的融合频率最高。这些融合蛋白均保留了完整的ZNF384结构,但融合伴侣则有不同程度的缺失,说明不同的ZNF384融合亚型之间具有相似的致AL发生发展机制。现有研究主要认为ZNF384融合蛋白通过染色质重塑调控下游蛋白的转录表达,在造血干细胞的分化、癌细胞的增殖凋亡和基因组修复中发挥潜在作用。ZNF384融合患者同时表达淋系和髓系特有的抗原,在疾病的进展中具有谱系转化特性,丰富的免疫表型给治疗方式带来了不确定性,并与融合亚型、发病年龄一起影响患者的临床结局。该文通过对近10年已发表的案例和大型队列研究进行统计归纳分析,进一步确认了ZNF384融合及其各亚型AL在现有研究背景下的发生频率,总结了已有的机制信息,并对不同治疗方式下ZNF384融合患者的预后作了简要分析,以期为后续针对这一独特亚型AL的诊疗和研究提供参考。展开更多
基金Supported by Ningbo Health Technology Project,Nos.2020Y12 and 2022Y12.
文摘Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byflow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and verified.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.
文摘由染色体易位引起的融合基因已成为白血病的主要致病因素。锌指蛋白384(zinc finger protein 384,ZNF384)融合作为急性白血病(acute leukemia,AL)中的非典型融合亚型,在不同的年龄群体中广泛发生。ZNF384具有丰富的融合伴侣,其中E1A结合蛋白p300(E1A binding protein p300,EP300)、转录因子3(transcription factor 3,TCF3)、TATA-box binding protein associated factor 15(TAF15)的融合频率最高。这些融合蛋白均保留了完整的ZNF384结构,但融合伴侣则有不同程度的缺失,说明不同的ZNF384融合亚型之间具有相似的致AL发生发展机制。现有研究主要认为ZNF384融合蛋白通过染色质重塑调控下游蛋白的转录表达,在造血干细胞的分化、癌细胞的增殖凋亡和基因组修复中发挥潜在作用。ZNF384融合患者同时表达淋系和髓系特有的抗原,在疾病的进展中具有谱系转化特性,丰富的免疫表型给治疗方式带来了不确定性,并与融合亚型、发病年龄一起影响患者的临床结局。该文通过对近10年已发表的案例和大型队列研究进行统计归纳分析,进一步确认了ZNF384融合及其各亚型AL在现有研究背景下的发生频率,总结了已有的机制信息,并对不同治疗方式下ZNF384融合患者的预后作了简要分析,以期为后续针对这一独特亚型AL的诊疗和研究提供参考。
