Aim: To evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects. Methods: A cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1 AY was used to i...Aim: To evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects. Methods: A cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1 AY was used to identify the differential gene expression profiles between the normal and azoospermic testes. cDNA probes were prepared by labeling mRNA from azoospermic and normal testicular tissues through reverse transcription with Cy5-dUTP and Cy3-dUTP, respectively. The mixed cDNA probes were then hybridized with cDNA microarray (each containing 4096 unique human cDNA sequences). The fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated. In situ hybridization was employed to detect the expression of RaplA in the testes of 10 fertile and 39 azoospermic subjects. Results: One hundred and twenty-eight differentially expressed genes were found to be possibly related to azoospermia, of which 56 were up-regulated and 72, down-regulated genes. The mRNA expression of RaplA in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes. Conclusion: Rap1A may play certain roles in the development of azoospermia.展开更多
Rap1A is a small G protein implicated in a spectrum of biological processes such as cell proliferation,adhesion,differentiation,and embryogenesis.The downstream effectors through which Rap1A mediates its diverse effec...Rap1A is a small G protein implicated in a spectrum of biological processes such as cell proliferation,adhesion,differentiation,and embryogenesis.The downstream effectors through which Rap1A mediates its diverse effects are largely unknown.Here we show that Rap1A,but not the related small G proteins Rap2 or Ras,binds the tumor suppressor Ras association domain family 1A(RASSF1A)in a manner that is regulated by phosphorylation of RASSF1A.Interaction with Rap1A is shown to influence the effect of RASSF1A on microtubule behavior.展开更多
白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿...白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.展开更多
BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To ...BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To investigate the expression and function of UCP1 in gastric cancer(GC).METHODS UCP1 protein expression in 211 GC tissues was examined using immunohisto-chemistry.Bisulfite sequencing PCR(BSP)was used to detect the methylation status of the UCP1 promoter in GC cell lines and tissues.The relationship between UCP1 expression and clinicopathological parameters was analyzed.CCK8,scratch,transwell,and flow cytometry assays were carried out to analyze the proliferation,migration,invasion,and apoptosis of GC cell lines after knockdown or overexpression of UCP1 in vitro.A nude mouse tumor xenograft model was used to investigate the function of UCP1 in vivo.RNA sequencing,Kyoto Ency-clopedia of Genes and Genomes analysis,and Rap1 pull-down assays were performed to identify the pathway associated with UCP1.RESULTS Loss of UCP1 was significantly associated with gender,poor differentiation,and advanced TNM stage of GC.Hypermethylation of UCP1 was confirmed in GC cells and tumor tissues by BSP.Overexpression of UCP1 suppressed GC cell proliferation,migration,and invasion,and it promoted apoptosis in vitro.UCP1 overexpression also suppressed GC tumor growth in vivo.Moreover,overexpression of UCP1 in GC cells resulted in a significant decrease in active Rap1 protein levels,whereas downregulation of UCP1 markedly enhanced Rap1 activity.CONCLUSION UCP1 downregulation in GC through promoter hypermethylation is related to the progression of GC,indicating that UCP1 plays a role as a tumor suppressor in GC.It regulates Rap1 signaling and may be a potential therapeutic target in GC.展开更多
目的探讨鸟嘌呤核苷酸交换因子C3G/Rap1酶和鸟嘌呤核苷酸交换因子Dock180/Rac1酶信号通路在卵巢癌浸润中的可能作用。方法 Western blot检测Dock180沉默的卵巢癌细胞SKOV3中C3G的表达,验证上皮性卵巢癌组织中Dock180与C3G的表达相关性;...目的探讨鸟嘌呤核苷酸交换因子C3G/Rap1酶和鸟嘌呤核苷酸交换因子Dock180/Rac1酶信号通路在卵巢癌浸润中的可能作用。方法 Western blot检测Dock180沉默的卵巢癌细胞SKOV3中C3G的表达,验证上皮性卵巢癌组织中Dock180与C3G的表达相关性;免疫组化比较卵巢癌组织中Dock180与C3G的表达趋势;免疫荧光观察SKOV3中Dock180与C3G及它们各自的下游蛋白Rac1/Rap1的定位。结果 Dock180基因沉默的细胞中C3G表达明显增强(P<0.05);Dock180与C3G在卵巢癌组织中的表达呈现相反趋势(P<0.05);C3G/Dock180均主要分布于细胞质,下游效应蛋白Rap1/Rac1在细胞膜和细胞质都有表达,但Rap1以细胞质为主,而Rac1可以伸展至细胞膜及细胞膜皱褶。结论卵巢癌细胞和组织中C3G与Dock180表达呈相反趋势,下游蛋白Rap1与Rac1在细胞内的定位分布差异,可能与C3G/Rap1和Dock180/Rac1信号通路在卵巢肿瘤浸润中的不同作用有关。展开更多
文摘Aim: To evaluate the Rap1A mRNA expression and its significance in the testes of normal and azoospermic subjects. Methods: A cDNA microarray that contained Rap1A and some other genes such as RBM, EIF1 AY was used to identify the differential gene expression profiles between the normal and azoospermic testes. cDNA probes were prepared by labeling mRNA from azoospermic and normal testicular tissues through reverse transcription with Cy5-dUTP and Cy3-dUTP, respectively. The mixed cDNA probes were then hybridized with cDNA microarray (each containing 4096 unique human cDNA sequences). The fluorescent signals were scanned and the values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated. In situ hybridization was employed to detect the expression of RaplA in the testes of 10 fertile and 39 azoospermic subjects. Results: One hundred and twenty-eight differentially expressed genes were found to be possibly related to azoospermia, of which 56 were up-regulated and 72, down-regulated genes. The mRNA expression of RaplA in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes. Conclusion: Rap1A may play certain roles in the development of azoospermia.
基金SKV also acknowledges the award of the Commonwealth Scholarship and the financial support received from the Department of Medical Oncology,Medical Sciences Division,The University of Oxford,Oxford,UK and the Cancer Research UK.
文摘Rap1A is a small G protein implicated in a spectrum of biological processes such as cell proliferation,adhesion,differentiation,and embryogenesis.The downstream effectors through which Rap1A mediates its diverse effects are largely unknown.Here we show that Rap1A,but not the related small G proteins Rap2 or Ras,binds the tumor suppressor Ras association domain family 1A(RASSF1A)in a manner that is regulated by phosphorylation of RASSF1A.Interaction with Rap1A is shown to influence the effect of RASSF1A on microtubule behavior.
基金supported by the National Natural Science Foundation of China(No.82160051,32100908)the Jiangxi Provincial Natural Science Foundation(No.20232BAB206018)+2 种基金the Science and Technology Research Project in the Education Department of Jiangxi Province,China(No.GJJ2200904)the Ph.D.Start-up Research Fund in Jiangxi University of Chinese Medicine(No.2020BSZR009)the Discipline of Chinese and Western Integrative Medicine in Jiangxi University of Chinese Medicine(No.zxyylxk20220103)。
文摘白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.
基金Supported by the Nanjing Health Science and Technology Development Fund,No.YKK24223.
文摘BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To investigate the expression and function of UCP1 in gastric cancer(GC).METHODS UCP1 protein expression in 211 GC tissues was examined using immunohisto-chemistry.Bisulfite sequencing PCR(BSP)was used to detect the methylation status of the UCP1 promoter in GC cell lines and tissues.The relationship between UCP1 expression and clinicopathological parameters was analyzed.CCK8,scratch,transwell,and flow cytometry assays were carried out to analyze the proliferation,migration,invasion,and apoptosis of GC cell lines after knockdown or overexpression of UCP1 in vitro.A nude mouse tumor xenograft model was used to investigate the function of UCP1 in vivo.RNA sequencing,Kyoto Ency-clopedia of Genes and Genomes analysis,and Rap1 pull-down assays were performed to identify the pathway associated with UCP1.RESULTS Loss of UCP1 was significantly associated with gender,poor differentiation,and advanced TNM stage of GC.Hypermethylation of UCP1 was confirmed in GC cells and tumor tissues by BSP.Overexpression of UCP1 suppressed GC cell proliferation,migration,and invasion,and it promoted apoptosis in vitro.UCP1 overexpression also suppressed GC tumor growth in vivo.Moreover,overexpression of UCP1 in GC cells resulted in a significant decrease in active Rap1 protein levels,whereas downregulation of UCP1 markedly enhanced Rap1 activity.CONCLUSION UCP1 downregulation in GC through promoter hypermethylation is related to the progression of GC,indicating that UCP1 plays a role as a tumor suppressor in GC.It regulates Rap1 signaling and may be a potential therapeutic target in GC.
文摘目的探讨鸟嘌呤核苷酸交换因子C3G/Rap1酶和鸟嘌呤核苷酸交换因子Dock180/Rac1酶信号通路在卵巢癌浸润中的可能作用。方法 Western blot检测Dock180沉默的卵巢癌细胞SKOV3中C3G的表达,验证上皮性卵巢癌组织中Dock180与C3G的表达相关性;免疫组化比较卵巢癌组织中Dock180与C3G的表达趋势;免疫荧光观察SKOV3中Dock180与C3G及它们各自的下游蛋白Rac1/Rap1的定位。结果 Dock180基因沉默的细胞中C3G表达明显增强(P<0.05);Dock180与C3G在卵巢癌组织中的表达呈现相反趋势(P<0.05);C3G/Dock180均主要分布于细胞质,下游效应蛋白Rap1/Rac1在细胞膜和细胞质都有表达,但Rap1以细胞质为主,而Rac1可以伸展至细胞膜及细胞膜皱褶。结论卵巢癌细胞和组织中C3G与Dock180表达呈相反趋势,下游蛋白Rap1与Rac1在细胞内的定位分布差异,可能与C3G/Rap1和Dock180/Rac1信号通路在卵巢肿瘤浸润中的不同作用有关。
