目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-...目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-Meier Plotter数据库中肝癌数据集,分析Rab40b和Rab40c的表达水平与肝癌患者预后的关系。结果肝癌组织中的Rab40a、Rab40al、Rab40b和Rab40c表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。Rab40c高表达与肝癌患者TNM分期可能存在相关性(P=0.064)。Rab40b、Rab40c高表达肝癌患者的总生存期(OS)、无复发生存期(RFS)短于Rab40b、Rab40c低表达肝癌患者,差异具有统计学意义(P<0.05)。肝癌组织中Rab40b的表达水平与肿瘤微环境的B细胞和CD8^(+)T细胞无关(P>0.05),而与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。肝癌组织中Rab40c的表达水平与肿瘤微环境的B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。结论Rab40家族在肝癌中高表达,尤其是Rab40b和Rab40c,通过影响肿瘤微环境中的免疫细胞促进肝癌的发生、发展,可作为肝癌治疗和预后的潜在生物标志物。展开更多
The insulin and 20-hydroxyecdysone(20E)pathways coordinately regulate in-sect vitellogenesis and ovarian development.However,the detailed molecular mechanisms such as the genes mediating the cooperation of the interac...The insulin and 20-hydroxyecdysone(20E)pathways coordinately regulate in-sect vitellogenesis and ovarian development.However,the detailed molecular mechanisms such as the genes mediating the cooperation of the interaction of these 2 pathways in reg-ulating insect reproductive development are not well understood.In the present study,a small GTPase,Rab4oC,was identified from the notorious agricultural pest Bactrocera dorsalis.In addition to the well-known RAB domain,it also has a unique SOCS-box do-main,which is different from other Rab-GTPases.Moreover,we found that Rab40C was enriched in the ovaries of sexually mature females.RNA interference(RNAi)-mediated knockdown of BdRab40C resulted in a decrease in vitellogenin synthesis,underdevel-oped ovaries,and low fertility.Furthermore,depletion of insulin receptor InR or the het-erodimer receptor of 20E(EcRor USP)by RNAi significantlydecreased the transcription of BdRab40C and resulted in lower fecundity.Further studies revealed that the transcrip-tion of BdRab40C could be upregulated by the injection of insulin or 20E.These results indicate that Rab40C participates in the insulin and 20E pathways to coordinately regulate reproduction in B.dorsalis.Our results not only provide new insights into the insulin-and 20E-stimulated regulatory pathways controlling female reproduction in insects but also contribute to the development of potential eco-friendly strategies for pest control.展开更多
文摘目的探讨Rab40家族在肝癌中的表达及临床意义。方法收集TIMER2.0数据库和The Human Protein Atlas数据库中肝癌数据集,分析Rab40家族在肝癌患者中的表达水平,并分析其表达与患者临床病理资料、肿瘤微环境免疫细胞浸润的关系;收集Kaplan-Meier Plotter数据库中肝癌数据集,分析Rab40b和Rab40c的表达水平与肝癌患者预后的关系。结果肝癌组织中的Rab40a、Rab40al、Rab40b和Rab40c表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。Rab40c高表达与肝癌患者TNM分期可能存在相关性(P=0.064)。Rab40b、Rab40c高表达肝癌患者的总生存期(OS)、无复发生存期(RFS)短于Rab40b、Rab40c低表达肝癌患者,差异具有统计学意义(P<0.05)。肝癌组织中Rab40b的表达水平与肿瘤微环境的B细胞和CD8^(+)T细胞无关(P>0.05),而与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。肝癌组织中Rab40c的表达水平与肿瘤微环境的B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关,差异具有统计学意义(P<0.05)。结论Rab40家族在肝癌中高表达,尤其是Rab40b和Rab40c,通过影响肿瘤微环境中的免疫细胞促进肝癌的发生、发展,可作为肝癌治疗和预后的潜在生物标志物。
基金supported by the National Key R&D Programof China(grant no.2019YFD1002100)National Natural Science Foundation of China(grant no.31471774)China Agriculture Research System of MOFandMARA(CARS-26).
文摘The insulin and 20-hydroxyecdysone(20E)pathways coordinately regulate in-sect vitellogenesis and ovarian development.However,the detailed molecular mechanisms such as the genes mediating the cooperation of the interaction of these 2 pathways in reg-ulating insect reproductive development are not well understood.In the present study,a small GTPase,Rab4oC,was identified from the notorious agricultural pest Bactrocera dorsalis.In addition to the well-known RAB domain,it also has a unique SOCS-box do-main,which is different from other Rab-GTPases.Moreover,we found that Rab40C was enriched in the ovaries of sexually mature females.RNA interference(RNAi)-mediated knockdown of BdRab40C resulted in a decrease in vitellogenin synthesis,underdevel-oped ovaries,and low fertility.Furthermore,depletion of insulin receptor InR or the het-erodimer receptor of 20E(EcRor USP)by RNAi significantlydecreased the transcription of BdRab40C and resulted in lower fecundity.Further studies revealed that the transcrip-tion of BdRab40C could be upregulated by the injection of insulin or 20E.These results indicate that Rab40C participates in the insulin and 20E pathways to coordinately regulate reproduction in B.dorsalis.Our results not only provide new insights into the insulin-and 20E-stimulated regulatory pathways controlling female reproduction in insects but also contribute to the development of potential eco-friendly strategies for pest control.
