Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties ...Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.展开更多
α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironme...α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.展开更多
Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts...Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.展开更多
BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-rel...BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.展开更多
Cells are capable of sensing and responding to the extracellular mechanical microenvironment via the actin skeleton.In vivo,tissues are frequently subject to mechanical forces,such as the rapid and significant shear f...Cells are capable of sensing and responding to the extracellular mechanical microenvironment via the actin skeleton.In vivo,tissues are frequently subject to mechanical forces,such as the rapid and significant shear flow encountered by vascular endothelial cells.However,the investigations about the transient response of intracellular actin networks under these intense external mechanical forces,their intrinsic mechanisms,and potential implications are very limited.Here,we observe that when cells are subject to the shear flow,an actin ring structure could be rapidly assembled at the periphery of the nucleus.To gain insights into the mechanism underlying this perinuclear actin ring assembly,we develop a computational model of actin dynamics.We demonstrate that this perinuclear actin ring assembly is triggered by the depolymerization of cortical actin,Arp2/3-dependent actin filament polymerization,and myosin-mediated actin network contraction.Furthermore,we discover that the compressive stress generated by the perinuclear actin ring could lead to a reduction in the nuclear spreading area,an increase in the nuclear height,and a decrease in the nuclear volume.The present model thus explains the mechanism of the perinuclear actin ring assembly under external mechanical forces and suggests that the spontaneous contraction of this actin structure can significantly impact nuclear morphology.展开更多
【目的】分析13种植物actin基因的密码子组成、密码子偏性及聚类关系,了解其密码子使用模式及影响密码子使用的因素,为深入研究分子进化及物种进化提供参考。【方法】运用Codon W 1.4.4软件分析13种植物的肌动蛋白基因（actin）密码子...【目的】分析13种植物actin基因的密码子组成、密码子偏性及聚类关系,了解其密码子使用模式及影响密码子使用的因素,为深入研究分子进化及物种进化提供参考。【方法】运用Codon W 1.4.4软件分析13种植物的肌动蛋白基因（actin）密码子组成及使用参数,并对影响密码子偏性的因素进行研究。应用MEGA 4.1对13条基因的CDS序列进行聚类分析,采用SPSS 20.0进行密码子偏性的聚类分析。【结果】双子叶植物中actin基因的GC含量为45.0%～51.2%、GC3s含量为36.3%～53.8%,单子叶植物中GC含量为53.0%～58.3%、GC3s含量为60.9%～75.8%;actin基因在单子叶植物中偏爱G/C结尾的密码子,双子叶植物中偏爱A/T结尾的密码子。GC和GC3s与有效密码子数（ENC）呈极显著负相关（P〈0.01）,相关系数均为-0.906。ENC绘图分析结果表明,actin基因密码子偏性同时受突变和选择压力影响,单子叶植物受选择压力影响的程度大于双子叶植物。基于actin基因密码子偏性的聚类将单子叶植物高粱、玉米聚为一类,水稻、大麦、竹聚为一类,8种双子叶植物聚为一类。【结论】actin基因密码子偏性与碱基组成密切相关,其密码子偏性在单、双子叶植物间存在差异,依据密码子偏性的聚类能在一定程度上反映物种间的亲缘关系。展开更多
文摘Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.
基金funded by National Nature Science Foundation of China (Grant Nos 30970705, 11172190, 81371171, and 81371172)
文摘α-smooth muscle actin （α-SMA） and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament （PDL） under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 （TGF-β1） and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells （hPDLCs）. The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.
基金supported by the National Natural Science Foundation of China(82171506 and 31872778)Discipline Innovative Engineering Plan(111 Program)of China(B13036)+3 种基金Key Laboratory Grant from Hunan Province(2016TP1006)Department of Science and Technology of Hunan Province(2021DK2001,Innovative Team Program 2019RS1010)Innovation-Driven Team Project from Central South University(2020CX016)Hunan Hundred Talents Program for Young Outstanding Scientists。
文摘Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.
文摘BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.
基金Project supported by the National Natural Science Foundation of China (Nos. 12025207 and 11872357)the Fundamental Research Funds for the Central Universities。
文摘Cells are capable of sensing and responding to the extracellular mechanical microenvironment via the actin skeleton.In vivo,tissues are frequently subject to mechanical forces,such as the rapid and significant shear flow encountered by vascular endothelial cells.However,the investigations about the transient response of intracellular actin networks under these intense external mechanical forces,their intrinsic mechanisms,and potential implications are very limited.Here,we observe that when cells are subject to the shear flow,an actin ring structure could be rapidly assembled at the periphery of the nucleus.To gain insights into the mechanism underlying this perinuclear actin ring assembly,we develop a computational model of actin dynamics.We demonstrate that this perinuclear actin ring assembly is triggered by the depolymerization of cortical actin,Arp2/3-dependent actin filament polymerization,and myosin-mediated actin network contraction.Furthermore,we discover that the compressive stress generated by the perinuclear actin ring could lead to a reduction in the nuclear spreading area,an increase in the nuclear height,and a decrease in the nuclear volume.The present model thus explains the mechanism of the perinuclear actin ring assembly under external mechanical forces and suggests that the spontaneous contraction of this actin structure can significantly impact nuclear morphology.
文摘【目的】分析13种植物actin基因的密码子组成、密码子偏性及聚类关系,了解其密码子使用模式及影响密码子使用的因素,为深入研究分子进化及物种进化提供参考。【方法】运用Codon W 1.4.4软件分析13种植物的肌动蛋白基因（actin）密码子组成及使用参数,并对影响密码子偏性的因素进行研究。应用MEGA 4.1对13条基因的CDS序列进行聚类分析,采用SPSS 20.0进行密码子偏性的聚类分析。【结果】双子叶植物中actin基因的GC含量为45.0%～51.2%、GC3s含量为36.3%～53.8%,单子叶植物中GC含量为53.0%～58.3%、GC3s含量为60.9%～75.8%;actin基因在单子叶植物中偏爱G/C结尾的密码子,双子叶植物中偏爱A/T结尾的密码子。GC和GC3s与有效密码子数（ENC）呈极显著负相关（P〈0.01）,相关系数均为-0.906。ENC绘图分析结果表明,actin基因密码子偏性同时受突变和选择压力影响,单子叶植物受选择压力影响的程度大于双子叶植物。基于actin基因密码子偏性的聚类将单子叶植物高粱、玉米聚为一类,水稻、大麦、竹聚为一类,8种双子叶植物聚为一类。【结论】actin基因密码子偏性与碱基组成密切相关,其密码子偏性在单、双子叶植物间存在差异,依据密码子偏性的聚类能在一定程度上反映物种间的亲缘关系。
