Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in ...Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.展开更多
Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by i...Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro.METHODS MTT colorimetric method was used to detect the influence of scutell...OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro.METHODS MTT colorimetric method was used to detect the influence of scutellarin on the survival rate of HCT116 cells.And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy.Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells.Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells.Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,p-YAP(Ser127),TAZ,and its downstream effector proteins c-Myc and cyclin D1,as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells.RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells.Hoechst33342/PI double staining showed that scutellarin effectively induced the apoptosis of HCT116 cells.Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,TAZ and its downstream effector proteins c-Myc,cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin,and the expression of p-YAP(ser127)was up-regulated.Moreover,scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2,and promoted the protein level of Bax.CONCLUSION Scutellarin may inhibit the proliferation and migration of HCT116 cells,while induce its apoptosis,potentially by activation of Hippo signaling pathway.展开更多
目的:探讨布托啡诺(BPH)对骨肉瘤(OS)细胞增殖、迁移和侵袭的影响及其相关的作用机制。方法:将MG-63细胞分为对照组、YAP抑制剂组(维替泊芬组)和BPH低、中、高浓度组,MTT法、克隆形成实验、FCM术、划痕愈合实验、Transwell实验、qPCR法...目的:探讨布托啡诺(BPH)对骨肉瘤(OS)细胞增殖、迁移和侵袭的影响及其相关的作用机制。方法:将MG-63细胞分为对照组、YAP抑制剂组(维替泊芬组)和BPH低、中、高浓度组,MTT法、克隆形成实验、FCM术、划痕愈合实验、Transwell实验、qPCR法、WB法和移植瘤实验分别检测处理后各组细胞的增殖活性、克隆形成数、细胞凋亡率、划痕愈合率,以及上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)、波形蛋白(vimentin)mRNA的表达和YAP、TAZ蛋白的表达,同时观察BPH和维替泊芬对移植瘤生长的影响。结果:与对照组相比,维替泊芬组和BPH低、中、高浓度组细胞增殖活性、克隆数、划痕愈合率、侵袭细胞数,以及N-cadherin和vimentin m RNA水平、YAP和TAZ蛋白表达及移植瘤体积均显著降低(均P<0.05),细胞凋亡率、E-cadherin mRNA水平及对移植瘤的抑瘤率均升高(均P<0.05),且BPH高浓度组与维替泊芬组之间各项指标均无明显差异(均P>0.05)。结论:BPH可能通过抑制Hippo/YAP信号通路来抑制OS细胞MG-63增殖、迁移和侵袭。展开更多
基金supported by the National Natural Science Foundation of China(81503187)。
文摘Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.
基金supported by the National Natural Science Fund(82004337)the Beijing University of Chinese Medicine new teacher launch fund(2020-JYB-XJSJJ-002)。
文摘Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
基金National Natural Science Foundation of China(81573813,81173598)Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447)+1 种基金Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917)and Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。
文摘OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro.METHODS MTT colorimetric method was used to detect the influence of scutellarin on the survival rate of HCT116 cells.And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy.Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells.Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells.Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,p-YAP(Ser127),TAZ,and its downstream effector proteins c-Myc and cyclin D1,as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells.RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells.Hoechst33342/PI double staining showed that scutellarin effectively induced the apoptosis of HCT116 cells.Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1,Lats1,YAP1,TAZ and its downstream effector proteins c-Myc,cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin,and the expression of p-YAP(ser127)was up-regulated.Moreover,scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2,and promoted the protein level of Bax.CONCLUSION Scutellarin may inhibit the proliferation and migration of HCT116 cells,while induce its apoptosis,potentially by activation of Hippo signaling pathway.
文摘目的:探讨布托啡诺(BPH)对骨肉瘤(OS)细胞增殖、迁移和侵袭的影响及其相关的作用机制。方法:将MG-63细胞分为对照组、YAP抑制剂组(维替泊芬组)和BPH低、中、高浓度组,MTT法、克隆形成实验、FCM术、划痕愈合实验、Transwell实验、qPCR法、WB法和移植瘤实验分别检测处理后各组细胞的增殖活性、克隆形成数、细胞凋亡率、划痕愈合率,以及上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)、波形蛋白(vimentin)mRNA的表达和YAP、TAZ蛋白的表达,同时观察BPH和维替泊芬对移植瘤生长的影响。结果:与对照组相比,维替泊芬组和BPH低、中、高浓度组细胞增殖活性、克隆数、划痕愈合率、侵袭细胞数,以及N-cadherin和vimentin m RNA水平、YAP和TAZ蛋白表达及移植瘤体积均显著降低(均P<0.05),细胞凋亡率、E-cadherin mRNA水平及对移植瘤的抑瘤率均升高(均P<0.05),且BPH高浓度组与维替泊芬组之间各项指标均无明显差异(均P>0.05)。结论:BPH可能通过抑制Hippo/YAP信号通路来抑制OS细胞MG-63增殖、迁移和侵袭。
