An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(...An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.展开更多
目的观察艾灸对结肠炎相关性结肠癌(CAC)大鼠的干预作用,从嘌呤受体P2X7R与Wnt/b-catenin信号通路探讨可能的效应机制。方法将SD大鼠随机分为正常组、CAC组、隔药灸组、隔姜灸组。CAC组、隔药灸组、隔姜灸组均采用腹腔注射AOM联合DSS法...目的观察艾灸对结肠炎相关性结肠癌(CAC)大鼠的干预作用,从嘌呤受体P2X7R与Wnt/b-catenin信号通路探讨可能的效应机制。方法将SD大鼠随机分为正常组、CAC组、隔药灸组、隔姜灸组。CAC组、隔药灸组、隔姜灸组均采用腹腔注射AOM联合DSS法制备CAC大鼠模型,隔药灸与隔姜灸组均取天枢(双)、气海穴进行治疗。记录各组大鼠体质量、疾病活动指数(DAI)和成瘤率;通过HE染色观察艾灸对CAC大鼠结肠损伤的干预效应;通过RT-q PCR和Western Blot技术,检测艾灸对CAC大鼠结肠组织C-myc、Wnt1、b-catenin、GSK-3bm RNA和P2X7R蛋白表达的调节作用。结果与正常组相比,CAC组大鼠体质量显著降低、DAI增高、成瘤率明显增加(P<0.05),结肠组织可见腺管共壁背靠背和筛样结构,高级别腺癌形成。CAC组大鼠结肠组织P2X7R蛋白表达显著下调(P<0.05),C-myc、b-catenin、GSK-3b、Wnt1 m RNA的表达均显著上调(P<0.05)。与CAC组相比,隔药灸组和隔姜灸组大鼠体质量增加,DAI降低(P<0.05),结肠组织P2X7R蛋白表达显著上调,C-myc m RNA下调(P<0.05);隔姜灸组成瘤率明显降低(P<0.05),且Wnt1、b-catenin、GSK-3bm RNA表达显著下调(P<0.05)。结论隔药灸、隔姜灸均能调节CAC大鼠结肠组织P2X7R及C-myc的异常表达,且隔姜灸还能下调CAC大鼠结肠组织Wnt1、b-catenin、GSK-3bm RNA的表达。展开更多
基金The Fund of National Cancer Center Research and Development(26-A-4),The Grants-in-Aid for Scientific Research(Grant Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.
文摘目的观察艾灸对结肠炎相关性结肠癌(CAC)大鼠的干预作用,从嘌呤受体P2X7R与Wnt/b-catenin信号通路探讨可能的效应机制。方法将SD大鼠随机分为正常组、CAC组、隔药灸组、隔姜灸组。CAC组、隔药灸组、隔姜灸组均采用腹腔注射AOM联合DSS法制备CAC大鼠模型,隔药灸与隔姜灸组均取天枢(双)、气海穴进行治疗。记录各组大鼠体质量、疾病活动指数(DAI)和成瘤率;通过HE染色观察艾灸对CAC大鼠结肠损伤的干预效应;通过RT-q PCR和Western Blot技术,检测艾灸对CAC大鼠结肠组织C-myc、Wnt1、b-catenin、GSK-3bm RNA和P2X7R蛋白表达的调节作用。结果与正常组相比,CAC组大鼠体质量显著降低、DAI增高、成瘤率明显增加(P<0.05),结肠组织可见腺管共壁背靠背和筛样结构,高级别腺癌形成。CAC组大鼠结肠组织P2X7R蛋白表达显著下调(P<0.05),C-myc、b-catenin、GSK-3b、Wnt1 m RNA的表达均显著上调(P<0.05)。与CAC组相比,隔药灸组和隔姜灸组大鼠体质量增加,DAI降低(P<0.05),结肠组织P2X7R蛋白表达显著上调,C-myc m RNA下调(P<0.05);隔姜灸组成瘤率明显降低(P<0.05),且Wnt1、b-catenin、GSK-3bm RNA表达显著下调(P<0.05)。结论隔药灸、隔姜灸均能调节CAC大鼠结肠组织P2X7R及C-myc的异常表达,且隔姜灸还能下调CAC大鼠结肠组织Wnt1、b-catenin、GSK-3bm RNA的表达。
