AUTHOR=Song Jingjing , Ni Chao , Dong Xubin , Sheng Chenang , Qu Yue , Zhu Libin 

TITLE=bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.988415

DOI=10.3389/fonc.2022.988415

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Neuroblastoma is the most common malignant extracranial tumor for children. Molecular mechanisms underpinning the pathogenesis of this disease are yet to be fully clarified. This study aimed to identify a novel oncogene that could be used as a biomarker informing the prognosis of neuroblastoma, and to predict its biological functions, using bioinformatics and molecular biology tools.</p></sec><sec><title>Methods</title><p>Three data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of <italic>bub1</italic> were compared, using the Kaplan-Meier curve and log-rank test. Immune infiltration was evaluated using ESTIMATE and MCP-counter algorithms. Synthetic small interfering RNAs (siRNAs) were employed to silence <italic>bub1</italic> expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of <italic>bub1</italic> were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.</p></sec><sec><title>Results</title><p>Expression of <italic>bub1</italic> was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of <italic>tpx2</italic> and the <italic>ASPM</italic> gene, and negatively correlate with host immune infiltration. Expression of <italic>bub1</italic> was elevated in patients with neuroblastoma. Silencing <italic>bub1</italic> expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (<italic>p</italic> &lt; 0.05), reduced migration (<italic>p</italic> &lt; 0.05), and increased apoptosis (<italic>p</italic> &lt; 0.05). Function analysis of <italic>bub1</italic> revealed cancer-promoting effects, probably <italic>via</italic> regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.</p></sec><sec><title>Conclusion</title><p>We identified a potential tumor-promoting gene <italic>bub1</italic> for neuroblastoma that could also serve as a prognostic biomarker.</p></sec>