Multi-omics study of BICD1 gene in promoting malignant progression of brain glioma
Objective To investigate the molecular mechanism of BICD1 gene promoting malignant progression of brain glioma based on spatial transcriptomic,single-cell sequencing data and RNA transcriptomic.Methods Public dataset of spatial transcriptome was employed to analyze the spatial distribution characteristics of BICD1 in normal brain tissues(sample:"248_C")and glioblastoma tissues(sample:"275_T").Single-cell sequencing data(from 6 148 cells of 14 patients)in Chinese Glioma Genome Atlas(CGGA)database were adopted to decipher the expression difference of BICD1 in different glioma cell types by R-language software.The biological functions of BICD1-related genes were analyzed based on RNA sequencing data in CGGA database(n=693)via the Kyoto Encyclopedia of Genes and Genomes(KEGG)and the Gene Ontology(GO)analyses.Results BICD1 was expressed in a wide range in normal brain tissues and specifically expressed at the boundary between glioma stem cells and tumor cells in glioblastoma tissues.Cell subtyping analyses based on single-cell sequencing data showed that BICD1 was highly expressed in astrocytes.In the Neftel subtyping system,cells with BICD1 highly expressed were mainly distributed in astrocytes-like cells and neural progenitor-like cells clusters.KEGG pathway analyses of BICD1-related differential genes showed that high expression of BICD1 was associated with enrichments of tumor-related biological functions such as cellular senescence(P=0.003),proteoglycans in cancer(P=0.004),and enrichments of intracellular transport processes such as actin cytoskeleton regulation(P=0.010).Low expression of BICD1 was associated with enrichments of ribosome-related functions(P＜0.001)and biological processes such as oxidative phosphorylation(P＜0.001).GO analyses of BICD 1-related differential genes showed that cytoplasmic translation(P＜0.001),ribosome small subunit assembly(P=0.001),regulation of chromosome separation(P=0.004)and chromosome separation(P=0.004)were significantly correlated with BICD1 expression levels.The expression level of BICD1 was significantly correlated with biological processes such as polyubiquitin modified-dependent protein binding(P=0.046),ubiquitin-ubiquitin ligase activity(P=0.033),negative regulation of protein depolymerization(P=0.010),monoubiquitinated protein deubiquitination(P=0.026),actin filament capping(P=0.007)and actin filament depolymerization(P=0.013).Conclusion BICD1 might be involved in protein ubiquitination degradation and cytoskeleton-related intracellular transport in precursor glioma cells,and plays a critical role in the malignant transformation of those cells by regulating biological processes such as cell senescence and cell division.
NETL
NSTL
万方数据
