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.
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