This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and Ju...This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014.Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues,CC cell lines,and normal cervical cells.Over-expression and silencing of RASAL2 were induced after transfection,and the migration,invasion,and proliferation of the CC cell lines were examined.Results:RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells,respectively.While low RASAL2 expression correlated with advanced stage and metastasis of CC,its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis.Under in vitro conditions,silencing of RASAL2 expression could significantly increase the proliferation,invasion,and migration of CC cells.Conclusion:RASAL2 functioned as a tumor suppressor in CC,and was down-regulated in CC tissue samples and cell lines.展开更多
目的通过生物数据库,综合分析Ras蛋白激活类似物1(ras protein activator like 1,RASAL1)和大鼠肉瘤蛋白活化因子2(ras protein activator like 2,RASAL2)在NSCLC中的表达及与临床预后的意义。方法全面检索Oncomine及Kaplan-Meier Plot...目的通过生物数据库,综合分析Ras蛋白激活类似物1(ras protein activator like 1,RASAL1)和大鼠肉瘤蛋白活化因子2(ras protein activator like 2,RASAL2)在NSCLC中的表达及与临床预后的意义。方法全面检索Oncomine及Kaplan-Meier Plotter数据库,分析RASAL1和RASAL2在NSCLC组织与正常组织中的表达差异及与患者临床预后的关系。结果 Oncomine数据库中分析发现,RASAL1在NSCLC中表达增高(P<0.05),RASAL2在NSCLC中表达降低(P <0.05)。Kaplan-Meier Plotter数据库分析发现,低表达的RASAL1和高表达的RASAL2在NSCLC中与良好的预后相关,且低表达的RASAL1与接受放化疗的NSCLC患者的良好预后相关。结论在NSCLC组织中RASAL1高表达,RASAL2低表达,且均与患者的预后相关。RASAL1可能作为促癌基因,RASAL2作为抑癌基因参与NSCLC的发生发展。RASAL1对NSCLC患者预后的影响还与放化疗效果相关,其可能是NSCLC的潜在治疗靶点。展开更多
Background and Aims:RAS protein activator like 2(RASAL2)is a newly discovered metabolic regulator involved in energy homeostasis and adipogenesis.However,whether RASAL2 is involved in hepatic lipid metabolism remains ...Background and Aims:RAS protein activator like 2(RASAL2)is a newly discovered metabolic regulator involved in energy homeostasis and adipogenesis.However,whether RASAL2 is involved in hepatic lipid metabolism remains undetermined.This study explored the function of RASAL2 and elucidated its potential mechanisms in nonalcoholic fatty liver disease(NAFLD).Methods:NAFLD models were established either by feeding mice a high-fat diet or by incubation of hepatocytes with 1 mM free fatty acids(oleic acid:palmitic acid=2:1).Pathological changes were observed by hematoxylin and eosin staining.Lipid accumulation was assessed by Oil Red O staining,BODIPY493/503 staining,and triglyceride quantification.The in vivo secretion rate of very lowdensity lipoprotein was determined by intravenous injection of tyloxapol.Gene regulation was analyzed by chromatin immunoprecipitation assays and hydroxymethylated DNA immunoprecipitation combined with real-time polymerase chain reaction.Results:RASAL2 deficiency ameliorated hepatic steatosis both in vivo and in vitro.Mechanistically,RASAL2 deficiency upregulated hepatic TET1 expression by activating the AKT signaling pathway and thereby promoted MTTP expression by DNA hydroxymethylation,leading to increased production and secretion of very low-density lipoprotein,which is the major carrier of triglycerides exported from the liver to distal tissues.Conclusions:Our study reports the first evidence that RASAL2 deficiency ameliorates hepatic steatosis by regulating lipid metabolism through the AKT/TET1/MTTP axis.These findings will help understand the pathogenesis of NAFLD and highlight the potency of RASAL2 as a new molecular target for NAFLD.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81572559)the Shandong Key Research and Development Plan(Grant No.2017CXGC1210).
文摘This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014.Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues,CC cell lines,and normal cervical cells.Over-expression and silencing of RASAL2 were induced after transfection,and the migration,invasion,and proliferation of the CC cell lines were examined.Results:RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells,respectively.While low RASAL2 expression correlated with advanced stage and metastasis of CC,its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis.Under in vitro conditions,silencing of RASAL2 expression could significantly increase the proliferation,invasion,and migration of CC cells.Conclusion:RASAL2 functioned as a tumor suppressor in CC,and was down-regulated in CC tissue samples and cell lines.
文摘目的通过生物数据库,综合分析Ras蛋白激活类似物1(ras protein activator like 1,RASAL1)和大鼠肉瘤蛋白活化因子2(ras protein activator like 2,RASAL2)在NSCLC中的表达及与临床预后的意义。方法全面检索Oncomine及Kaplan-Meier Plotter数据库,分析RASAL1和RASAL2在NSCLC组织与正常组织中的表达差异及与患者临床预后的关系。结果 Oncomine数据库中分析发现,RASAL1在NSCLC中表达增高(P<0.05),RASAL2在NSCLC中表达降低(P <0.05)。Kaplan-Meier Plotter数据库分析发现,低表达的RASAL1和高表达的RASAL2在NSCLC中与良好的预后相关,且低表达的RASAL1与接受放化疗的NSCLC患者的良好预后相关。结论在NSCLC组织中RASAL1高表达,RASAL2低表达,且均与患者的预后相关。RASAL1可能作为促癌基因,RASAL2作为抑癌基因参与NSCLC的发生发展。RASAL1对NSCLC患者预后的影响还与放化疗效果相关,其可能是NSCLC的潜在治疗靶点。
基金supported by National Natural Science Foundation of China (grant number 82070591)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (grant number 2017BT01S131)Postdoctoral Science Foundation of China (grant number 2018M641919).
文摘Background and Aims:RAS protein activator like 2(RASAL2)is a newly discovered metabolic regulator involved in energy homeostasis and adipogenesis.However,whether RASAL2 is involved in hepatic lipid metabolism remains undetermined.This study explored the function of RASAL2 and elucidated its potential mechanisms in nonalcoholic fatty liver disease(NAFLD).Methods:NAFLD models were established either by feeding mice a high-fat diet or by incubation of hepatocytes with 1 mM free fatty acids(oleic acid:palmitic acid=2:1).Pathological changes were observed by hematoxylin and eosin staining.Lipid accumulation was assessed by Oil Red O staining,BODIPY493/503 staining,and triglyceride quantification.The in vivo secretion rate of very lowdensity lipoprotein was determined by intravenous injection of tyloxapol.Gene regulation was analyzed by chromatin immunoprecipitation assays and hydroxymethylated DNA immunoprecipitation combined with real-time polymerase chain reaction.Results:RASAL2 deficiency ameliorated hepatic steatosis both in vivo and in vitro.Mechanistically,RASAL2 deficiency upregulated hepatic TET1 expression by activating the AKT signaling pathway and thereby promoted MTTP expression by DNA hydroxymethylation,leading to increased production and secretion of very low-density lipoprotein,which is the major carrier of triglycerides exported from the liver to distal tissues.Conclusions:Our study reports the first evidence that RASAL2 deficiency ameliorates hepatic steatosis by regulating lipid metabolism through the AKT/TET1/MTTP axis.These findings will help understand the pathogenesis of NAFLD and highlight the potency of RASAL2 as a new molecular target for NAFLD.
