Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and ident...Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of b展开更多
More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ,...More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.展开更多
目的:检测Hippo-YAP信号通路中主要效应蛋白Yes相关蛋白(Yes-associated protein,YAP)在正常胰腺组织和胰腺癌组织中的表达,探讨其表达强度与临床病理因素之间的关系及意义.方法:应用免疫组织化学EnVision法测定Hippo信号通路中YAP蛋白...目的:检测Hippo-YAP信号通路中主要效应蛋白Yes相关蛋白(Yes-associated protein,YAP)在正常胰腺组织和胰腺癌组织中的表达,探讨其表达强度与临床病理因素之间的关系及意义.方法:应用免疫组织化学EnVision法测定Hippo信号通路中YAP蛋白在45例胰腺癌及15例正常胰腺组织中的表达,应用RT-PCR方法检测YAP mRNA在45例胰腺癌及15例正常胰腺组织中的表达.结果:胰腺癌组织中YAP蛋白主要表达于胰腺导管上皮细胞,45例胰腺癌组织中YAP的阳性表达率为93.33%(42/45),15例正常胰腺组织中YAP阳性表达率为26.67%(4/15),两组间的表达差异具有统计学意义(2=27.95,P<0.01).在胰腺癌组织中YAP的表达与肿瘤分化程度密切相关(P=0.048),与年龄、性别、吸烟、饮酒、肥胖、糖耐量异常、糖尿病、慢性胰腺炎及临床分期等无关(P值分别是0.577、0.565、0.541、0.224、1.000、0.542、0.555、0.571、0.926).胰腺癌患者血清CA19-9水平与胰腺癌组织中YAP阳性程度呈正相关.YAP m R N A在胰腺癌组织中的表达较正常胰腺组织明显升高(0.3682±0.0783 vs 0.0394±0.0091,P<0.01).结论:Hippo-YAP通路可能在胰腺癌的发生、发展中发挥重要作用.并有可能成为胰腺癌治疗中新的靶点.展开更多
基金supported by the National Natural Science Foundation of China,No.81330042,81620108018(both to SQF),and 81702147(to ZJW)
文摘Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of b
基金General Research Fund(No.2140855RGC Reference No.CUHK14114414)from The Research Grants Council of Hong Kong+1 种基金National Natural Science Grant No.81201591 from ChinaDirect Grant for Research No.2014.2.002 from The Chinese University of Hong Kong
文摘More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.
文摘目的:检测Hippo-YAP信号通路中主要效应蛋白Yes相关蛋白(Yes-associated protein,YAP)在正常胰腺组织和胰腺癌组织中的表达,探讨其表达强度与临床病理因素之间的关系及意义.方法:应用免疫组织化学EnVision法测定Hippo信号通路中YAP蛋白在45例胰腺癌及15例正常胰腺组织中的表达,应用RT-PCR方法检测YAP mRNA在45例胰腺癌及15例正常胰腺组织中的表达.结果:胰腺癌组织中YAP蛋白主要表达于胰腺导管上皮细胞,45例胰腺癌组织中YAP的阳性表达率为93.33%(42/45),15例正常胰腺组织中YAP阳性表达率为26.67%(4/15),两组间的表达差异具有统计学意义(2=27.95,P<0.01).在胰腺癌组织中YAP的表达与肿瘤分化程度密切相关(P=0.048),与年龄、性别、吸烟、饮酒、肥胖、糖耐量异常、糖尿病、慢性胰腺炎及临床分期等无关(P值分别是0.577、0.565、0.541、0.224、1.000、0.542、0.555、0.571、0.926).胰腺癌患者血清CA19-9水平与胰腺癌组织中YAP阳性程度呈正相关.YAP m R N A在胰腺癌组织中的表达较正常胰腺组织明显升高(0.3682±0.0783 vs 0.0394±0.0091,P<0.01).结论:Hippo-YAP通路可能在胰腺癌的发生、发展中发挥重要作用.并有可能成为胰腺癌治疗中新的靶点.
