Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by gr...Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by graded expression of the Shh and 5’Hox genes,the regulatory mechanisms underlying anterior digit development,especially digit I(DI),remain poorly defined.This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods,including humans,which exerted an inhibitory effect on skeletal development.Zic3 was highly expressed in the anterior region of limb buds at early developmental stages,with species-specific divergence emerging during later development.Overexpression of Zic3 significantly delayed chondrogenesis and ossification,leading to bone shortening but not loss.Furthermore,RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development,including Cytl1,Sox9,Ihh,Ptch1,Runx2,and Wnt16.These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.展开更多
目的研究ZIC5(Zic family member 5)在前列腺癌中的异常表达及其对前列腺癌生物学表型的影响。方法实时荧光定量聚合酶链式反应(quantitative real-time PCR)检测ZIC5在前列腺癌组织标本和对应癌旁正常组织、PC3和LNCa P细胞株及正常前...目的研究ZIC5(Zic family member 5)在前列腺癌中的异常表达及其对前列腺癌生物学表型的影响。方法实时荧光定量聚合酶链式反应(quantitative real-time PCR)检测ZIC5在前列腺癌组织标本和对应癌旁正常组织、PC3和LNCa P细胞株及正常前列腺上皮中的表达水平。siRNA干扰ZIC5后,CCK-8法和Transwell试验检测前列腺癌细胞PC3和LNCa P的增殖、迁移和侵袭。生物信息学分析可能调控ZIC5的miRNA并进行验证。结果 ZIC5在前列腺癌组织中表达水平上升(t=4.2,P<0.001),并且与Gleason评分分级具有相关性(P<0.05),在前列腺癌细胞株中表达水平显著高于正常前列腺癌上皮(P<0.01)。前列腺癌细胞株PC3和LNCa P中siRNA干扰ZIC5 24 h后,细胞增殖减慢,迁移和侵袭能力被抑制。生物信息学及双荧光素酶报告显示,ZIC5受miR-449家族调控,ZIC5与miR-449家族在前列腺癌标本中表达水平呈负相关(ZIC5 vs miR-449a:r=-0.64,P<0.05,ZIC5 vs miR-449b,r=-0.52,P<0.05),双荧光素酶报告基因检测显示miR-449家族结合ZIC5 3’UTR。异常表达的ZIC5可激活EMT通路,干扰ZIC5和过表达miR-449可抑制ZIC5蛋白表达,并逆转前列腺癌细胞中EMT状态。结论 ZIC5受miR-449家族调控,促进前列腺癌生长和侵袭。展开更多
ZIC1(zinc finger of the cerebellum 1)基因是一种重要的肿瘤相关基因。近年来研究发现ZIC1基因在多种恶性肿瘤中都有表达并与肿瘤的发生、发展密切相关,但其具体的作用机制仍未完全阐明。随着对ZIC1基因研究的进一步深入,其有可能为...ZIC1(zinc finger of the cerebellum 1)基因是一种重要的肿瘤相关基因。近年来研究发现ZIC1基因在多种恶性肿瘤中都有表达并与肿瘤的发生、发展密切相关,但其具体的作用机制仍未完全阐明。随着对ZIC1基因研究的进一步深入,其有可能为肿瘤的早期诊断、基因治疗和预后评估提供新的思路。展开更多
基金supported by the Department of Science&Technology of Liaoning Province(2024-MS-099,2024-BS-093)。
文摘Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by graded expression of the Shh and 5’Hox genes,the regulatory mechanisms underlying anterior digit development,especially digit I(DI),remain poorly defined.This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods,including humans,which exerted an inhibitory effect on skeletal development.Zic3 was highly expressed in the anterior region of limb buds at early developmental stages,with species-specific divergence emerging during later development.Overexpression of Zic3 significantly delayed chondrogenesis and ossification,leading to bone shortening but not loss.Furthermore,RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development,including Cytl1,Sox9,Ihh,Ptch1,Runx2,and Wnt16.These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.
文摘目的研究ZIC5(Zic family member 5)在前列腺癌中的异常表达及其对前列腺癌生物学表型的影响。方法实时荧光定量聚合酶链式反应(quantitative real-time PCR)检测ZIC5在前列腺癌组织标本和对应癌旁正常组织、PC3和LNCa P细胞株及正常前列腺上皮中的表达水平。siRNA干扰ZIC5后,CCK-8法和Transwell试验检测前列腺癌细胞PC3和LNCa P的增殖、迁移和侵袭。生物信息学分析可能调控ZIC5的miRNA并进行验证。结果 ZIC5在前列腺癌组织中表达水平上升(t=4.2,P<0.001),并且与Gleason评分分级具有相关性(P<0.05),在前列腺癌细胞株中表达水平显著高于正常前列腺癌上皮(P<0.01)。前列腺癌细胞株PC3和LNCa P中siRNA干扰ZIC5 24 h后,细胞增殖减慢,迁移和侵袭能力被抑制。生物信息学及双荧光素酶报告显示,ZIC5受miR-449家族调控,ZIC5与miR-449家族在前列腺癌标本中表达水平呈负相关(ZIC5 vs miR-449a:r=-0.64,P<0.05,ZIC5 vs miR-449b,r=-0.52,P<0.05),双荧光素酶报告基因检测显示miR-449家族结合ZIC5 3’UTR。异常表达的ZIC5可激活EMT通路,干扰ZIC5和过表达miR-449可抑制ZIC5蛋白表达,并逆转前列腺癌细胞中EMT状态。结论 ZIC5受miR-449家族调控,促进前列腺癌生长和侵袭。
文摘ZIC1(zinc finger of the cerebellum 1)基因是一种重要的肿瘤相关基因。近年来研究发现ZIC1基因在多种恶性肿瘤中都有表达并与肿瘤的发生、发展密切相关,但其具体的作用机制仍未完全阐明。随着对ZIC1基因研究的进一步深入,其有可能为肿瘤的早期诊断、基因治疗和预后评估提供新的思路。
