Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long...Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies.Studies have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be characterized.Therefore,our study aimed to explore the role and underlying mechanism of SNHG4 in GC.Methods:We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells.Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients.Cellular function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and invasion.We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth.Mechanically,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC patients.SNHG4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro.The in vivo experiment indicated that SNHG4 facilitated GC tumor growth.Furthermore,SNHG4 was demonstrated to bind to miR-409-3p.Moreover,CREB1 was directly targeted by miR-409-3p.Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy.Additionally,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1.Conclusion:In conclusion,we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1,which may deepen the understanding of the underlying mechanism in GC development.展开更多
目的:研究丙戊酸钠对大鼠海马神经元癫痫样放电后磷酸化腺感苷反应元件结合蛋白1(Phosphorylated cAMP responsive element binding protein 1,P-CREB1)表达的影响。方法:wistar新生鼠,迅速断头取脑,体外培养海马神经元,建立神经元癫痫...目的:研究丙戊酸钠对大鼠海马神经元癫痫样放电后磷酸化腺感苷反应元件结合蛋白1(Phosphorylated cAMP responsive element binding protein 1,P-CREB1)表达的影响。方法:wistar新生鼠,迅速断头取脑,体外培养海马神经元,建立神经元癫痫样放电模型,将神经元分为空白组、模型组、丙戊酸钠低剂量(50mg/L)组、丙戊酸钠高剂量(100mg/L)组,运用免疫荧光技术观察P-CREB1在神经元癫痫样放电后在细胞内的表达部位,采用wester blot技术测定P-CREB1在不同分组中的表达强度。结果:通过免疫荧光技术,在各组中都可以看到P-CREB1在细胞核内表达,以模型组最明显;运用Western blot,发现表达趋势与免疫荧光一致,并且,给予丙戊酸钠后,P-CREB1表达减弱,且高剂量组与低剂量组之间差异有统计学意义(P<0.05)。结论:海马神经元无镁处理后呈癫痫样放电,同时P-CREB1被过度激活,而有效浓度的丙戊酸钠可抑制此反应P-CREB1的磷酸化水平。展开更多
文摘Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality worldwide.Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy.Long non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies.Studies have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be characterized.Therefore,our study aimed to explore the role and underlying mechanism of SNHG4 in GC.Methods:We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells.Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients.Cellular function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and invasion.We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth.Mechanically,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC patients.SNHG4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro.The in vivo experiment indicated that SNHG4 facilitated GC tumor growth.Furthermore,SNHG4 was demonstrated to bind to miR-409-3p.Moreover,CREB1 was directly targeted by miR-409-3p.Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy.Additionally,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1.Conclusion:In conclusion,we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1,which may deepen the understanding of the underlying mechanism in GC development.
文摘目的:研究丙戊酸钠对大鼠海马神经元癫痫样放电后磷酸化腺感苷反应元件结合蛋白1(Phosphorylated cAMP responsive element binding protein 1,P-CREB1)表达的影响。方法:wistar新生鼠,迅速断头取脑,体外培养海马神经元,建立神经元癫痫样放电模型,将神经元分为空白组、模型组、丙戊酸钠低剂量(50mg/L)组、丙戊酸钠高剂量(100mg/L)组,运用免疫荧光技术观察P-CREB1在神经元癫痫样放电后在细胞内的表达部位,采用wester blot技术测定P-CREB1在不同分组中的表达强度。结果:通过免疫荧光技术,在各组中都可以看到P-CREB1在细胞核内表达,以模型组最明显;运用Western blot,发现表达趋势与免疫荧光一致,并且,给予丙戊酸钠后,P-CREB1表达减弱,且高剂量组与低剂量组之间差异有统计学意义(P<0.05)。结论:海马神经元无镁处理后呈癫痫样放电,同时P-CREB1被过度激活,而有效浓度的丙戊酸钠可抑制此反应P-CREB1的磷酸化水平。
