Fosl2属于转录因子AP-1(activator protein 1)家族中Fos亚家族中的一个成员。Fos亚家族蛋白的成员有c-Fos、Fosl1、Fosl2及FosB。Fos家族蛋白与Jun家族成员蛋白以同源或异源二聚体的形式结合DNA靶序列后被称为转录因子AP-1,参与靶基因...Fosl2属于转录因子AP-1(activator protein 1)家族中Fos亚家族中的一个成员。Fos亚家族蛋白的成员有c-Fos、Fosl1、Fosl2及FosB。Fos家族蛋白与Jun家族成员蛋白以同源或异源二聚体的形式结合DNA靶序列后被称为转录因子AP-1,参与靶基因调节。Fosl2参与恒定NK细胞分化、巨噬细胞极化、B细胞发育、炎性因子分泌和骨稳态调控。研究表明其可诱导表皮分化、保持皮肤屏障功能从而防止银屑病的发生,并且与TGF-β1相互调节而参与硬皮病等疾病,另外,Fosl2可能参与到酚类抗氧化剂预防肿瘤的机制中。随着研究的开展,Fosl2在更多不同疾病中的作用也逐渐被揭示,如乳腺癌的发生发展及转移、炎症所致的纤维化等。因此,调控Fosl2活性或功能或可成为未来开发自身免疫性疾病药物的靶点之一。展开更多
Activating protein-1(AP-1)composed of Jun and Fos family proteins,which are frequently activated by pathogens to induce cellular inflammation and immune responses.In this study,by using RNA sequencing(RNA-seq)technolo...Activating protein-1(AP-1)composed of Jun and Fos family proteins,which are frequently activated by pathogens to induce cellular inflammation and immune responses.In this study,by using RNA sequencing(RNA-seq)technology,we found that FosB,Fosl2,and JunD expression was co-induced 12 and 20 h in grass carp(Ctenopharyngodon idella)kidney cell line(CIK cells)after grass carp reovirus(GCRV)infection.Full-length cDNA of the three genes were cloned and phylogenetic analysis indicated that the corresponding proteins shared high homology with those in higher vertebrates.The tissue distribution analysis of the three genes showed they were ubiquitously expressed in various tissues of healthy grass carp.In infection assay,FosB,Fosl2,and JunD were up-regulated and co-expressed 8 h after GCRV infection in CIK cells.Protein interaction and co-expression network analysis revealed that FosB,Fosl2,and JunD showed similar functions and were co-expressed in mammals and fish.Taken together,these results indicated that the co-expression of the AP-1 family proteins in grass carp uniformly responds to GCRV infection.These findings provided insights into the further study of AP-1 transcription factors function during grass carp reovirus infection.展开更多
目的·研究微小RNA-143(miR-143)在人结肠癌及癌周正常组织中的表达,探索其对结肠癌HCT116、RKO细胞功能的影响及下游靶基因的预测。方法·设计合成并构建miR-143慢病毒表达载体,稳定转染人结肠癌HCT116、RKO细胞。实时荧光定量...目的·研究微小RNA-143(miR-143)在人结肠癌及癌周正常组织中的表达,探索其对结肠癌HCT116、RKO细胞功能的影响及下游靶基因的预测。方法·设计合成并构建miR-143慢病毒表达载体,稳定转染人结肠癌HCT116、RKO细胞。实时荧光定量PCR检测人结肠癌、癌周正常组织、慢病毒感染后HCT116和RKO细胞中miR-143的表达。Annexin V-APC单染法及流式细胞仪检测感染前后细胞凋亡能力。Transwell法检测感染前后HCT116、RKO细胞迁移能力的改变。Western blotting方法检测FOSL2蛋白的表达。结果·miR-143在结肠癌组织中的表达量显著低于癌周正常组织(0.339±0.454 vs 1.003±0.003)(U=16.000,Z=-4.231,P=0.000)。上调miR-143后,HCT116细胞凋亡率显著高于阴性对照组(P=0.000),RKO细胞凋亡率显著高于阴性对照组(P=0.000)。上调miR-143后,HCT116迁移细胞数显著低于阴性对照组(P=0.000)。miR-143下调后,RKO迁移细胞数显著高于阴性对照组(P=0.003)。miR-143下调后,FOSL2蛋白表达量升高。结论·miR-143在结肠癌组织中表达量显著下降。上调miR-143可促进结肠癌细胞凋亡,并抑制HCT116细胞迁移;下调miR-143可促进RKO细胞迁移;抑制miR-143功能可上调FOSL2蛋白表达。展开更多
Natural killer(NK)cells are essential in controlling cancer and infection.However,little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation.In this study,we applied ...Natural killer(NK)cells are essential in controlling cancer and infection.However,little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation.In this study,we applied the assay of transposase accessible chromatin with sequencing(ATAC-seq)technique in a home-developed in vitro NK cell differentiation system.Analysis of ATAC-seq data illustrated two distinct transcription factor(TF)clusters that dynamically regulate NK cell differentiation.Moreover,two TFs from the second cluster,FOS-like 2(FOSL2)and early growth response 2(EGR2),were identified as novel essential TFs that control NK cell maturation and function.Knocking down either of these two TFs significantly impacted NK cell differentiation.Finally,we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation.展开更多
文摘Fosl2属于转录因子AP-1(activator protein 1)家族中Fos亚家族中的一个成员。Fos亚家族蛋白的成员有c-Fos、Fosl1、Fosl2及FosB。Fos家族蛋白与Jun家族成员蛋白以同源或异源二聚体的形式结合DNA靶序列后被称为转录因子AP-1,参与靶基因调节。Fosl2参与恒定NK细胞分化、巨噬细胞极化、B细胞发育、炎性因子分泌和骨稳态调控。研究表明其可诱导表皮分化、保持皮肤屏障功能从而防止银屑病的发生,并且与TGF-β1相互调节而参与硬皮病等疾病,另外,Fosl2可能参与到酚类抗氧化剂预防肿瘤的机制中。随着研究的开展,Fosl2在更多不同疾病中的作用也逐渐被揭示,如乳腺癌的发生发展及转移、炎症所致的纤维化等。因此,调控Fosl2活性或功能或可成为未来开发自身免疫性疾病药物的靶点之一。
基金This work was supported by the National Natural Science Foundation of China(grant number 31672690)the Earmarked Fund for China Agriculture Research System(grant number CARS-45-19).
文摘Activating protein-1(AP-1)composed of Jun and Fos family proteins,which are frequently activated by pathogens to induce cellular inflammation and immune responses.In this study,by using RNA sequencing(RNA-seq)technology,we found that FosB,Fosl2,and JunD expression was co-induced 12 and 20 h in grass carp(Ctenopharyngodon idella)kidney cell line(CIK cells)after grass carp reovirus(GCRV)infection.Full-length cDNA of the three genes were cloned and phylogenetic analysis indicated that the corresponding proteins shared high homology with those in higher vertebrates.The tissue distribution analysis of the three genes showed they were ubiquitously expressed in various tissues of healthy grass carp.In infection assay,FosB,Fosl2,and JunD were up-regulated and co-expressed 8 h after GCRV infection in CIK cells.Protein interaction and co-expression network analysis revealed that FosB,Fosl2,and JunD showed similar functions and were co-expressed in mammals and fish.Taken together,these results indicated that the co-expression of the AP-1 family proteins in grass carp uniformly responds to GCRV infection.These findings provided insights into the further study of AP-1 transcription factors function during grass carp reovirus infection.
文摘目的·研究微小RNA-143(miR-143)在人结肠癌及癌周正常组织中的表达,探索其对结肠癌HCT116、RKO细胞功能的影响及下游靶基因的预测。方法·设计合成并构建miR-143慢病毒表达载体,稳定转染人结肠癌HCT116、RKO细胞。实时荧光定量PCR检测人结肠癌、癌周正常组织、慢病毒感染后HCT116和RKO细胞中miR-143的表达。Annexin V-APC单染法及流式细胞仪检测感染前后细胞凋亡能力。Transwell法检测感染前后HCT116、RKO细胞迁移能力的改变。Western blotting方法检测FOSL2蛋白的表达。结果·miR-143在结肠癌组织中的表达量显著低于癌周正常组织(0.339±0.454 vs 1.003±0.003)(U=16.000,Z=-4.231,P=0.000)。上调miR-143后,HCT116细胞凋亡率显著高于阴性对照组(P=0.000),RKO细胞凋亡率显著高于阴性对照组(P=0.000)。上调miR-143后,HCT116迁移细胞数显著低于阴性对照组(P=0.000)。miR-143下调后,RKO迁移细胞数显著高于阴性对照组(P=0.003)。miR-143下调后,FOSL2蛋白表达量升高。结论·miR-143在结肠癌组织中表达量显著下降。上调miR-143可促进结肠癌细胞凋亡,并抑制HCT116细胞迁移;下调miR-143可促进RKO细胞迁移;抑制miR-143功能可上调FOSL2蛋白表达。
基金supported by the National Key R&D Program of China(Grant No.2017YFA0102900)to KQthe National Natural Science Foundation of China(Grant Nos.91640113,91940306,31771428,and 31970858 to KQ,as well as 81330071 to HW)supported by the Fundamental Research Funds for the Central Universities,China(Grant Nos.YD2070002019,WK2070000158,and WK9110000141)to KQ。
文摘Natural killer(NK)cells are essential in controlling cancer and infection.However,little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation.In this study,we applied the assay of transposase accessible chromatin with sequencing(ATAC-seq)technique in a home-developed in vitro NK cell differentiation system.Analysis of ATAC-seq data illustrated two distinct transcription factor(TF)clusters that dynamically regulate NK cell differentiation.Moreover,two TFs from the second cluster,FOS-like 2(FOSL2)and early growth response 2(EGR2),were identified as novel essential TFs that control NK cell maturation and function.Knocking down either of these two TFs significantly impacted NK cell differentiation.Finally,we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation.
