Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that ...Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.展开更多
Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and ...Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression.Therefore,we selected them for this present study,where the effects of bone marrow mesenchymal stem cell-derived EVs(BMSDs-EVs)enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition(EMT)and stemness maintenance in TC.The under-expression of GTF2I and FAT1 was validated in TC cell lines.Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells,EMT,and stemness maintenance.Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression.MSC-EVs could shuttle GTF2I into TPC-1 cells,where GTF2I inhibited TC malignant phenotypes,EMT,and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation.In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice.Taken together,our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.展开更多
Thymic epithelial tumors(TETs)comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features.Owing to their rare nature,the molecular cla...Thymic epithelial tumors(TETs)comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features.Owing to their rare nature,the molecular classification of TETs has only recently begun to be fully explored.The advent of advanced molecular studies,particularly the ability to sequence the DNA and RNA of tumors in a massively parallel fashion,has led to an increased understanding of the molecular underpinnings of thymic neoplasia.Thymomas,characterized by a heterogeneous group of molecular alterations,tend to have low mutational burdens and various copy number abnormalities including a characteristic loss of chromosomal material in the region of 6q25.2-p25.3,a recurrent,specific point mutation GTF2I p.L424H,and specific expression of certain microRNAs.Thymic carcinomas,in contrast,are generally characterized by increased tumor mutational burdens,multiple copy number alterations,and varied,non-recurrent,somatic mutations.Advances in molecular knowledge of TETs allow for more precise molecular classification of these tumors,and the presence of specific alterations aids in the diagnosis of borderline lesions.In the future,additional molecular studies will better delineate the molecular landscape of these tumors and may one day allow for more targeted treatment algorithms.This review aims to cover the current understanding of the molecular alterations thus far identified in thymomas and thymic carcinomas.展开更多
基金supported by the National Natural Science Foundation of China,No.81271321(to HYZ)a grant from the Department of Science and Technology Research Projects in Sichuan Province of China,No.2013FZ0015(to HYZ)the Fundamental Research Funds for the Central Universities,China,No.2017SCU11049(to QZ)
文摘Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.
基金supported by Shanghai Shenkang Hospital Development Center(No.SHDC12019X38).
文摘Through bioinformatics predictions,we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma(TC).Further,Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression.Therefore,we selected them for this present study,where the effects of bone marrow mesenchymal stem cell-derived EVs(BMSDs-EVs)enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition(EMT)and stemness maintenance in TC.The under-expression of GTF2I and FAT1 was validated in TC cell lines.Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells,EMT,and stemness maintenance.Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression.MSC-EVs could shuttle GTF2I into TPC-1 cells,where GTF2I inhibited TC malignant phenotypes,EMT,and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation.In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice.Taken together,our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
文摘Thymic epithelial tumors(TETs)comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features.Owing to their rare nature,the molecular classification of TETs has only recently begun to be fully explored.The advent of advanced molecular studies,particularly the ability to sequence the DNA and RNA of tumors in a massively parallel fashion,has led to an increased understanding of the molecular underpinnings of thymic neoplasia.Thymomas,characterized by a heterogeneous group of molecular alterations,tend to have low mutational burdens and various copy number abnormalities including a characteristic loss of chromosomal material in the region of 6q25.2-p25.3,a recurrent,specific point mutation GTF2I p.L424H,and specific expression of certain microRNAs.Thymic carcinomas,in contrast,are generally characterized by increased tumor mutational burdens,multiple copy number alterations,and varied,non-recurrent,somatic mutations.Advances in molecular knowledge of TETs allow for more precise molecular classification of these tumors,and the presence of specific alterations aids in the diagnosis of borderline lesions.In the future,additional molecular studies will better delineate the molecular landscape of these tumors and may one day allow for more targeted treatment algorithms.This review aims to cover the current understanding of the molecular alterations thus far identified in thymomas and thymic carcinomas.
