目的基于数据库分析ADD3基因在弥漫性大B细胞淋巴瘤(Diffuse Large B Cell Lymphoma,DLBCL)中的表达情况及临床意义。方法基于Oncomine数据库进行荟萃分析,筛选出在DLBCL中的差异表达基因ADD3,并进一步分析其在mRNA及DNA水平上的表达差...目的基于数据库分析ADD3基因在弥漫性大B细胞淋巴瘤(Diffuse Large B Cell Lymphoma,DLBCL)中的表达情况及临床意义。方法基于Oncomine数据库进行荟萃分析,筛选出在DLBCL中的差异表达基因ADD3,并进一步分析其在mRNA及DNA水平上的表达差异,从GEO数据库下载含有DLBCL患者信息的数据集,对ADD3的表达量与患者的预后进行生存分析,并进一步对年龄、性别等亚组进行分析。利用GEPIA2在线分析工具对DLBCL样本中ADD3与c-Myc、Blc2、P53等基因进行相关性分析,通过癌症基因图谱数据库分析网站(UALCAN)对ADD3在DLBCL患者中的表达进行验证分析,DLBCL中ADD3在性别、年龄、种族、疾病阶段等不同亚组的表达量进一步进行验证分析。结果ADD3在荟萃分析中位于显著低表达基因的104位,生存分析显示ADD3的表达量与患者的生存预后显著正相关,相关性研究显示ADD3与Bcl2、c-Myc、P53等基因呈现弱相关性,亚组分析显示ADD3的表达量与性别、种族等因素无关,21~40岁年龄组表达量均高于41~60岁、61~80岁、81~100岁年龄组,对年龄亚组进一步进行生存分析,结果显示ADD3低表达组预后更差,与先前的分析结果一致。结论ADD3在DLBCL中低表达,且与患者预后呈现显著正相关性,有望作为DLBCL的独立预后标志物,为治疗和DLBCL提供参考靶点。展开更多
Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-...Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer.Howeve-r,little is known about the functional targets and regulatory mechanism of QKI-5.Here,we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3(ADD3)significantly correlates with a poor prognosis in lung cancer.QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14.Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis,we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner.By binding to multiple sites in an upstream intron region,QKI-5 represses the splicing of ADD3 exon 14.We also identified several QKI mutations in tumors,which cause dysregulation of the splicing of QKI targets ADD3 and NUMB.Taken together,our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event,which underlies in part the tumor suppressor function of QKI.展开更多
Additive manufacturing(AM),interchangeably termed as3D printing(3DP),has been defined as one of the key technologies in the national development strategies of a number of countries around the world.America Makes,as th...Additive manufacturing(AM),interchangeably termed as3D printing(3DP),has been defined as one of the key technologies in the national development strategies of a number of countries around the world.America Makes,as the National Additive Manufacturing Innovation Institute,is the nation’s leading and collaborative partner in AM/3DP technology research,discovery,creation,and innovation,working efficiently to innovate and accelerate AM/3DP to increase America’s global manufacturing competitiveness(https://americamakes.us).German展开更多
文摘目的基于数据库分析ADD3基因在弥漫性大B细胞淋巴瘤(Diffuse Large B Cell Lymphoma,DLBCL)中的表达情况及临床意义。方法基于Oncomine数据库进行荟萃分析,筛选出在DLBCL中的差异表达基因ADD3,并进一步分析其在mRNA及DNA水平上的表达差异,从GEO数据库下载含有DLBCL患者信息的数据集,对ADD3的表达量与患者的预后进行生存分析,并进一步对年龄、性别等亚组进行分析。利用GEPIA2在线分析工具对DLBCL样本中ADD3与c-Myc、Blc2、P53等基因进行相关性分析,通过癌症基因图谱数据库分析网站(UALCAN)对ADD3在DLBCL患者中的表达进行验证分析,DLBCL中ADD3在性别、年龄、种族、疾病阶段等不同亚组的表达量进一步进行验证分析。结果ADD3在荟萃分析中位于显著低表达基因的104位,生存分析显示ADD3的表达量与患者的生存预后显著正相关,相关性研究显示ADD3与Bcl2、c-Myc、P53等基因呈现弱相关性,亚组分析显示ADD3的表达量与性别、种族等因素无关,21~40岁年龄组表达量均高于41~60岁、61~80岁、81~100岁年龄组,对年龄亚组进一步进行生存分析,结果显示ADD3低表达组预后更差,与先前的分析结果一致。结论ADD3在DLBCL中低表达,且与患者预后呈现显著正相关性,有望作为DLBCL的独立预后标志物,为治疗和DLBCL提供参考靶点。
基金This work was supported by the National Natural Science Foundation of China(31661143035,31770881,and 32071288)the National Basic Research Program of China(2017YFA0504400)to J.H.
文摘Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer.Howeve-r,little is known about the functional targets and regulatory mechanism of QKI-5.Here,we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3(ADD3)significantly correlates with a poor prognosis in lung cancer.QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14.Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis,we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner.By binding to multiple sites in an upstream intron region,QKI-5 represses the splicing of ADD3 exon 14.We also identified several QKI mutations in tumors,which cause dysregulation of the splicing of QKI targets ADD3 and NUMB.Taken together,our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event,which underlies in part the tumor suppressor function of QKI.
基金supported by the National Natural Science Foundation of China (51575267 and 51322509)the National Key Research and Development Program ‘‘Additive Manufacturing and Laser Manufacturing’’ (2016YFB1100101)+5 种基金the Top-Notch Young Talents Program of China, the NSFC-DFG Sino-German Research Project (GZ 1217)the Key Research and Development Program of Jiangsu Provincial Department of Science and Technology of China (BE2016181)the 333 High-level Talents Training Project (BRA2015368), the Aeronautical Science Foundation of China (2015ZE52051)the Outstanding Youth Foundation of Jiangsu Province of China (BK20130035)the Program for New Century Excellent Talents in University (NCET-13-0854)the Fundamental Research Funds for the Central Universities (NE2013103, NP2015206 and NZ2016108)
文摘Additive manufacturing(AM),interchangeably termed as3D printing(3DP),has been defined as one of the key technologies in the national development strategies of a number of countries around the world.America Makes,as the National Additive Manufacturing Innovation Institute,is the nation’s leading and collaborative partner in AM/3DP technology research,discovery,creation,and innovation,working efficiently to innovate and accelerate AM/3DP to increase America’s global manufacturing competitiveness(https://americamakes.us).German
