R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signa...R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signaling,which has now been acknowledged in numerous in vitro and in vivo studies.Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer.Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks.Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types,particularly CRC.As a critical regulator of the Wnt pathway,it modulates several phenotypes of cells,such as cell proliferation,invasion,migration,and cancer stem cell properties.Recently,RSPO mutations,gene rearrangements,fusions,copy number alterations,and altered gene expression have also been identified in a variety of cancers,including CRC.In this review,we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC.In addition to the compelling physiological and biological roles in cellular fate and regulation,we propose that RSPO2 would be valuable as a potential biomarker for prognostic,diagnostic,and therapeutic use in CRC.展开更多
为探究特异性顶部盘状底板反应蛋白2(RSPO2)在2种绵羊皮肤中的差异表达及其对毛囊生长相关基因表达的影响,以美利奴羊和小尾寒羊背部皮肤为材料,利用免疫组织化学、实时荧光定量PCR技术和Western-blot技术检测RSPO2在美利奴羊和小尾寒...为探究特异性顶部盘状底板反应蛋白2(RSPO2)在2种绵羊皮肤中的差异表达及其对毛囊生长相关基因表达的影响,以美利奴羊和小尾寒羊背部皮肤为材料,利用免疫组织化学、实时荧光定量PCR技术和Western-blot技术检测RSPO2在美利奴羊和小尾寒羊背部皮肤毛囊中的表达与定位;在皮肤成纤维细胞中过表达和干扰RSPO2,用实时荧光定量PCR和Western-blot检测毛囊生长相关基因及增殖相关基因的表达。结果显示,RSPO2 m RNA和蛋白在美利奴羊和小尾寒羊中均有表达,且美利奴羊中的表达量极显著高于小尾寒羊(P<0.01)。在成纤维细胞中转染过表达RSPO2载体后,β-连环蛋白(β-catenin)和Lef1 m RNA和蛋白的表达量极显著升高(P<0.01),BMP4和TGF-β1 m RNA和蛋白的表达量极显著降低(P<0.01);在成纤维细胞中转染干扰RSPO2载体后,β-catenin和Lef1 m RNA和蛋白的表达量极显著降低(P<0.01),BMP4和TGF-β1 m RNA和蛋白的表达量极显著升高(P<0.01)。同时,试验证实RSPO2可以促进成纤维细胞的增殖。结果表明,RSPO2对绵羊毛囊生长有一定的作用,可能是通过促进成纤维细胞增殖和调控参与毛囊生长相关基因的表达来实现的。展开更多
文摘R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway.Among the R-spondin family,RSPO2 has emanated as a novel regulator of Wnt signaling,which has now been acknowledged in numerous in vitro and in vivo studies.Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer.Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks.Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types,particularly CRC.As a critical regulator of the Wnt pathway,it modulates several phenotypes of cells,such as cell proliferation,invasion,migration,and cancer stem cell properties.Recently,RSPO mutations,gene rearrangements,fusions,copy number alterations,and altered gene expression have also been identified in a variety of cancers,including CRC.In this review,we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC.In addition to the compelling physiological and biological roles in cellular fate and regulation,we propose that RSPO2 would be valuable as a potential biomarker for prognostic,diagnostic,and therapeutic use in CRC.
文摘为探究特异性顶部盘状底板反应蛋白2(RSPO2)在2种绵羊皮肤中的差异表达及其对毛囊生长相关基因表达的影响,以美利奴羊和小尾寒羊背部皮肤为材料,利用免疫组织化学、实时荧光定量PCR技术和Western-blot技术检测RSPO2在美利奴羊和小尾寒羊背部皮肤毛囊中的表达与定位;在皮肤成纤维细胞中过表达和干扰RSPO2,用实时荧光定量PCR和Western-blot检测毛囊生长相关基因及增殖相关基因的表达。结果显示,RSPO2 m RNA和蛋白在美利奴羊和小尾寒羊中均有表达,且美利奴羊中的表达量极显著高于小尾寒羊(P<0.01)。在成纤维细胞中转染过表达RSPO2载体后,β-连环蛋白(β-catenin)和Lef1 m RNA和蛋白的表达量极显著升高(P<0.01),BMP4和TGF-β1 m RNA和蛋白的表达量极显著降低(P<0.01);在成纤维细胞中转染干扰RSPO2载体后,β-catenin和Lef1 m RNA和蛋白的表达量极显著降低(P<0.01),BMP4和TGF-β1 m RNA和蛋白的表达量极显著升高(P<0.01)。同时,试验证实RSPO2可以促进成纤维细胞的增殖。结果表明,RSPO2对绵羊毛囊生长有一定的作用,可能是通过促进成纤维细胞增殖和调控参与毛囊生长相关基因的表达来实现的。
