简介：AbstractObjective:To investigate the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias.Methods:We examined the overlap of genetically associated genes among NTDs, CHDs, and hypospadias. We then compared the expression profiles of these diseases based on all the detected genes and disease-associated TFs. The differentially expressed TFs that we obtained were further subjected to functional enrichment analysis to elucidate their role in the development of these birth defects.Results:TF genes were significantly enriched in complex birth defects (P= 5.95 × 10-24). NTDs, CHDs, and hypospadias showed distinct gene expression profiles compared with the controls. Although TFs could not efficiently separate CHDs from normal subjects, distinct gene expression profiles of TFs could distinguish NTDs and hypospadias from controls. Differentially expressed TFs can be used to characterize NTDs, hypospadias, and controls. The enriched TFs in biological processes (BPs) reflected the different morphological processes of NTDs, CHDs, and hypospadias.Conclusions:This study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through the related BPs. The investigation of genetically associated genes and gene expression profiles for the three different complex birth defects provides new insights into how the dysregulation of TFs influences their developmental process.

简介：AbstractBackground:Glioma is a common malignant brain tumor. The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and Western blotting. Cell proliferation was assessed using the CCK8 assay. Transwell and wound healing assays were utilized to evaluate cell migration. Additionally, cell cycle and apoptosis were detected using flow cytometry.Results:We observed that the expression level of SPI1 was up-regulated in glioma tissues, compared to normal tissues. Furthermore, we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro. Flow cytometry results demonstrate that, compared to si-NC cells, si-SPI1 cells stagnated in the G1 phase, and downregulation of SPI1 expression is able to increase rates of apoptosis. Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS.Conclusions:Our results suggest that SPI1 can promote proliferation and migration of glioma. Furthermore, SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.