Objectives:NOD-like receptor family pyrin domain-containing(NLRP)1-mediated pyroptosis plays a key role in the pathogenesis of cerebral ischemia-reperfusion injury(CIRI).C-Myc is reported to play a major role in CIRI....Objectives:NOD-like receptor family pyrin domain-containing(NLRP)1-mediated pyroptosis plays a key role in the pathogenesis of cerebral ischemia-reperfusion injury(CIRI).C-Myc is reported to play a major role in CIRI.However,the mechanism remains unclear.This study aimed to investigate whether c-Myc affects CIRI by regulating Serine/Arginine-rich Splicing Factor 1(SRSF1)/NLRP1-mediated pyroptosis.Methods:Oxygen-glucose deprivation/reperfusion(OGD/R)induced neuroblastoma cells for the establishment of an in vitro CIRI model.The levels of c-Myc and SRSF1,cell viability,the expression of pyroptosis-related factors,and the interaction between SRSF1 and NLRP1 were evaluated.Results:The expression of c-Myc and SRSF1 was decreased in OGD/R-induced neuroblastoma cells.c-Myc overexpression increased c-Myc and SRSF1 expression and cell viability in OGD/Rinduced neuroblastoma cells while inhibiting NLRP1,Caspase1,apoptosis-associated speck-like protein containing a CARD(ASC),interleukin-1beta(IL-1β),IL-18,and lactate dehydrogenase levels and pyroptosis.C-Myc was positively correlated with SRSF1.SRSF1 low expression reversed the effects of c-Myc on the above indicators in OGD/Rinduced neuroblastoma cells.Mechanically,SRSF1 interacted with NLRP1.SRSF1 was negatively correlated with NLRP1.The NLRP1 activator muramyl dipeptide(MDP)reversed the SRSF1 effect on OGD/R-induced neuroblastoma cells.Conclusion:Our results indicated that c-Myc reduced OGD/R-induced neuroblastoma cell pyroptosis by inhibiting NLRP1 activation by positive feedback SRSF1 signal.Our findings suggested that the c-Myc/SRSF1 axis might be a new strategy for treating CIRI in the clinic.展开更多
[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达...[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达或敲低SRSF2或GLI1后,检测HER2阳性乳腺癌细胞SKBR-3、HCC1419、AU-565的侵袭细胞数。敲低SRSF2后分析GLI1的剪接形式,并且过表达GLI1不同剪接形式(fGLI1和tGLI1)后检测HER2阳性乳腺癌细胞的侵袭细胞数。[结果]在TCGA和GEO数据集中,与正常组织相比,HER2阳性乳腺癌组织中SRSF2的mRNA表达上升5倍(1.00±0.05 vs 5.74±0.37,P<0.05)。同时,SRSF2高表达的HER2阳性乳腺癌患者具有更短的无远处转移生存(P<0.05)。过表达SRSF2后,HER2阳性乳腺癌细胞的侵袭细胞数上升2倍(152.88±25.15个vs 376.47±32.31个,P<0.05)。敲低SRSF2后,HER2阳性乳腺癌细胞中fGLI1的mRNA表达上升,tGLI1的mRNA表达下降。过表达tGLI1后,HER2阳性乳腺癌细胞的侵袭细胞数上升3倍(147.43±21.99个vs 397.42±34.03个,P<0.05)。[结论]SRSF2通过选择性剪接将GLI1剪接成tGLI1的形式后,可促进HER2阳性乳腺癌的侵袭能力(152.88±25.15 vs 376.47±32.31,P<0.05)。展开更多
人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的...人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的相对表达，包括表达量或翻译后修饰［2］。富含丝氨酸／精氨酸剪接因子1（SRSF1），是1个典型富含丝氨酸／精氨酸SR蛋白家族成员，参与基因组成性剪接和选择性剪接［3］。SRSF1通过调节基因选择性剪接参与肿瘤形成发展。展开更多
基金supported by a fund from the Hainan Provincial Natural Science Foundation of China(No.821MS156).
文摘Objectives:NOD-like receptor family pyrin domain-containing(NLRP)1-mediated pyroptosis plays a key role in the pathogenesis of cerebral ischemia-reperfusion injury(CIRI).C-Myc is reported to play a major role in CIRI.However,the mechanism remains unclear.This study aimed to investigate whether c-Myc affects CIRI by regulating Serine/Arginine-rich Splicing Factor 1(SRSF1)/NLRP1-mediated pyroptosis.Methods:Oxygen-glucose deprivation/reperfusion(OGD/R)induced neuroblastoma cells for the establishment of an in vitro CIRI model.The levels of c-Myc and SRSF1,cell viability,the expression of pyroptosis-related factors,and the interaction between SRSF1 and NLRP1 were evaluated.Results:The expression of c-Myc and SRSF1 was decreased in OGD/R-induced neuroblastoma cells.c-Myc overexpression increased c-Myc and SRSF1 expression and cell viability in OGD/Rinduced neuroblastoma cells while inhibiting NLRP1,Caspase1,apoptosis-associated speck-like protein containing a CARD(ASC),interleukin-1beta(IL-1β),IL-18,and lactate dehydrogenase levels and pyroptosis.C-Myc was positively correlated with SRSF1.SRSF1 low expression reversed the effects of c-Myc on the above indicators in OGD/Rinduced neuroblastoma cells.Mechanically,SRSF1 interacted with NLRP1.SRSF1 was negatively correlated with NLRP1.The NLRP1 activator muramyl dipeptide(MDP)reversed the SRSF1 effect on OGD/R-induced neuroblastoma cells.Conclusion:Our results indicated that c-Myc reduced OGD/R-induced neuroblastoma cell pyroptosis by inhibiting NLRP1 activation by positive feedback SRSF1 signal.Our findings suggested that the c-Myc/SRSF1 axis might be a new strategy for treating CIRI in the clinic.
文摘[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中,分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达或敲低SRSF2或GLI1后,检测HER2阳性乳腺癌细胞SKBR-3、HCC1419、AU-565的侵袭细胞数。敲低SRSF2后分析GLI1的剪接形式,并且过表达GLI1不同剪接形式(fGLI1和tGLI1)后检测HER2阳性乳腺癌细胞的侵袭细胞数。[结果]在TCGA和GEO数据集中,与正常组织相比,HER2阳性乳腺癌组织中SRSF2的mRNA表达上升5倍(1.00±0.05 vs 5.74±0.37,P<0.05)。同时,SRSF2高表达的HER2阳性乳腺癌患者具有更短的无远处转移生存(P<0.05)。过表达SRSF2后,HER2阳性乳腺癌细胞的侵袭细胞数上升2倍(152.88±25.15个vs 376.47±32.31个,P<0.05)。敲低SRSF2后,HER2阳性乳腺癌细胞中fGLI1的mRNA表达上升,tGLI1的mRNA表达下降。过表达tGLI1后,HER2阳性乳腺癌细胞的侵袭细胞数上升3倍(147.43±21.99个vs 397.42±34.03个,P<0.05)。[结论]SRSF2通过选择性剪接将GLI1剪接成tGLI1的形式后,可促进HER2阳性乳腺癌的侵袭能力(152.88±25.15 vs 376.47±32.31,P<0.05)。
文摘人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的相对表达，包括表达量或翻译后修饰［2］。富含丝氨酸／精氨酸剪接因子1（SRSF1），是1个典型富含丝氨酸／精氨酸SR蛋白家族成员，参与基因组成性剪接和选择性剪接［3］。SRSF1通过调节基因选择性剪接参与肿瘤形成发展。
