bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma

BackgroundNeuroblastoma 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 neuroblas...

Full description

Bibliographic Details
Main Authors: Jingjing Song, Chao Ni, Xubin Dong, Chenang Sheng, Yue Qu, Libin Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.988415/full
_version_ 1828373050303709184
author Jingjing Song
Jingjing Song
Chao Ni
Xubin Dong
Chenang Sheng
Yue Qu
Libin Zhu
author_facet Jingjing Song
Jingjing Song
Chao Ni
Xubin Dong
Chenang Sheng
Yue Qu
Libin Zhu
author_sort Jingjing Song
collection DOAJ
description BackgroundNeuroblastoma 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.MethodsThree data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of bub1 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 bub1 expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of bub1 were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsExpression of bub1 was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of tpx2 and the ASPM gene, and negatively correlate with host immune infiltration. Expression of bub1 was elevated in patients with neuroblastoma. Silencing bub1 expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (p < 0.05), reduced migration (p < 0.05), and increased apoptosis (p < 0.05). Function analysis of bub1 revealed cancer-promoting effects, probably via regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.ConclusionWe identified a potential tumor-promoting gene bub1 for neuroblastoma that could also serve as a prognostic biomarker.
first_indexed 2024-04-14T07:12:40Z
format Article
id doaj.art-6de5025bc14c410fbb95e33b36d2c685
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-04-14T07:12:40Z
publishDate 2022-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-6de5025bc14c410fbb95e33b36d2c6852022-12-22T02:06:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.988415988415bub1 as a potential oncogene and a prognostic biomarker for neuroblastomaJingjing Song0Jingjing Song1Chao Ni2Xubin Dong3Chenang Sheng4Yue Qu5Libin Zhu6Department of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Allergy and Immunology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaSecond Clinical College, Wenzhou Medical University, Wenzhou, ChinaDepartment of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Medical University-Monash Biomedicine Discovery Institute (BDI) Alliance in Clinical and Experimental Biomedicine, Wenzhou, ChinaDepartment of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaBackgroundNeuroblastoma 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.MethodsThree data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of bub1 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 bub1 expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of bub1 were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsExpression of bub1 was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of tpx2 and the ASPM gene, and negatively correlate with host immune infiltration. Expression of bub1 was elevated in patients with neuroblastoma. Silencing bub1 expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (p < 0.05), reduced migration (p < 0.05), and increased apoptosis (p < 0.05). Function analysis of bub1 revealed cancer-promoting effects, probably via regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.ConclusionWe identified a potential tumor-promoting gene bub1 for neuroblastoma that could also serve as a prognostic biomarker.https://www.frontiersin.org/articles/10.3389/fonc.2022.988415/fullbub1neuroblastomaoncogeneimmunityprognosisbiomarker
spellingShingle Jingjing Song
Jingjing Song
Chao Ni
Xubin Dong
Chenang Sheng
Yue Qu
Libin Zhu
bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
Frontiers in Oncology
bub1
neuroblastoma
oncogene
immunity
prognosis
biomarker
title bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
title_full bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
title_fullStr bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
title_full_unstemmed bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
title_short bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
title_sort bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
topic bub1
neuroblastoma
oncogene
immunity
prognosis
biomarker
url https://www.frontiersin.org/articles/10.3389/fonc.2022.988415/full
work_keys_str_mv AT jingjingsong bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT jingjingsong bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT chaoni bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT xubindong bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT chenangsheng bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT yuequ bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma
AT libinzhu bub1asapotentialoncogeneandaprognosticbiomarkerforneuroblastoma