目的探讨威灵仙总皂苷通过调控微小RNA(miRNA)-410-3p对胶质瘤细胞生物学活性的影响以及对第10号染色体缺失的磷酸酶和张力蛋白同源物基因/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(phosphatase and tensin homolog deleted on chromosome ten...目的探讨威灵仙总皂苷通过调控微小RNA(miRNA)-410-3p对胶质瘤细胞生物学活性的影响以及对第10号染色体缺失的磷酸酶和张力蛋白同源物基因/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin,PTEN/Akt/mTOR)信号通路的调节作用。方法用不同浓度威灵仙总皂苷处理U87细胞后,用CCK-8法检测细胞存活率。将对数生长期U87细胞随机分为对照组、NC组(转染miR-410-3p NC)、inhibitor组(转染miR-410-3p inhibitor)以及inhibitor联合威灵仙总皂苷组(转染miR-410-3p inhibitor 24 h后,40μmol·L^(-1)威灵仙总皂苷处理),依次检测miR-410-3p表达水平、细胞存活率、细胞迁移和侵袭力,miR-410-3p与PTEN的靶向关系和PTEN、p-Akt、Akt、p-mTOR以及mTOR蛋白的相对表达量。结果细胞存活率随威灵仙总皂苷浓度的升高而降低(P<0.05);与NC组比较,inhibitor组划痕愈合率、侵袭细胞数量、p-Akt和p-mTOR蛋白的相对表达量升高,miR-410-3p表达水平以及PTEN蛋白的相对表达量降低(P<0.05);与inhibitor组比较,inhibitor联合威灵仙总皂苷组细胞存活率、划痕愈合率、侵袭细胞数量、p-Akt和p-mTOR蛋白相对表达量降低,miR-410-3p表达水平以及PTEN蛋白相对表达量升高(P<0.05)。结论威灵仙总皂苷可抑制胶质瘤细胞的恶性生物学行为,其可能是通过上调miR-410-3p表达,进而调控PTEN/Akt/mTOR信号通路发挥作用。展开更多
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
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.
