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HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2

Neuroblastoma (NB) is the most common solid tumor apart from central nervous system malignancies in children aged 0–14 years, and the outcomes of high-risk patients are dismal. High mobility group box 3 (HMGB3) plays an oncogenic role in many cancers; however, its biological role in NB is still uncl...

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Autores principales: Zhong, Xiaodan, Zhang, Songling, Zhang, Yutong, Jiang, Zongmiao, Li, Yanan, Chang, Jian, Niu, Junqi, Shi, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721485/
https://www.ncbi.nlm.nih.gov/pubmed/34988076
http://dx.doi.org/10.3389/fcell.2021.769547
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author Zhong, Xiaodan
Zhang, Songling
Zhang, Yutong
Jiang, Zongmiao
Li, Yanan
Chang, Jian
Niu, Junqi
Shi, Ying
author_facet Zhong, Xiaodan
Zhang, Songling
Zhang, Yutong
Jiang, Zongmiao
Li, Yanan
Chang, Jian
Niu, Junqi
Shi, Ying
author_sort Zhong, Xiaodan
collection PubMed
description Neuroblastoma (NB) is the most common solid tumor apart from central nervous system malignancies in children aged 0–14 years, and the outcomes of high-risk patients are dismal. High mobility group box 3 (HMGB3) plays an oncogenic role in many cancers; however, its biological role in NB is still unclear. Using data mining, we found that HMGB3 expression was markedly elevated in NB patients with unfavorable prognoses. When HMGB3 expression in NB cell lines was inhibited, cell proliferation, migration, and invasion were suppressed, and HMGB3 knockdown inhibited NB tumor development in mice. RT−PCR was employed to detect mRNA expression of nine coexpressed genes in response to HMGB3 knockdown, and TPX2 was identified. Furthermore, overexpression of TPX2 reversed the cell proliferation effect of HMGB3 silencing. Multivariate Cox regression analysis indicated that HMGB3 and TPX2 might be independent prognostic factors for overall survival and event-free survival, which showed the highest significance (p < 0.001). According to the nomogram predictor constructed, the integration of gene expression and clinicopathological features exhibited better prognostic prediction power. Furthermore, the random forest algorithm and receiver operating characteristic curves also showed that HMGB3 and TPX2 played important roles in discriminating the vital status (alive/dead) of patients in the NB datasets. Our informatics analysis and biological experiments suggested that HMGB3 is correlated with the unfavorable clinical outcomes of NB, and plays an important role in promoting cell growth, proliferation, and invasion in NB, potentially representing a new therapeutic target for tumor progression.
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spelling pubmed-87214852022-01-04 HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2 Zhong, Xiaodan Zhang, Songling Zhang, Yutong Jiang, Zongmiao Li, Yanan Chang, Jian Niu, Junqi Shi, Ying Front Cell Dev Biol Cell and Developmental Biology Neuroblastoma (NB) is the most common solid tumor apart from central nervous system malignancies in children aged 0–14 years, and the outcomes of high-risk patients are dismal. High mobility group box 3 (HMGB3) plays an oncogenic role in many cancers; however, its biological role in NB is still unclear. Using data mining, we found that HMGB3 expression was markedly elevated in NB patients with unfavorable prognoses. When HMGB3 expression in NB cell lines was inhibited, cell proliferation, migration, and invasion were suppressed, and HMGB3 knockdown inhibited NB tumor development in mice. RT−PCR was employed to detect mRNA expression of nine coexpressed genes in response to HMGB3 knockdown, and TPX2 was identified. Furthermore, overexpression of TPX2 reversed the cell proliferation effect of HMGB3 silencing. Multivariate Cox regression analysis indicated that HMGB3 and TPX2 might be independent prognostic factors for overall survival and event-free survival, which showed the highest significance (p < 0.001). According to the nomogram predictor constructed, the integration of gene expression and clinicopathological features exhibited better prognostic prediction power. Furthermore, the random forest algorithm and receiver operating characteristic curves also showed that HMGB3 and TPX2 played important roles in discriminating the vital status (alive/dead) of patients in the NB datasets. Our informatics analysis and biological experiments suggested that HMGB3 is correlated with the unfavorable clinical outcomes of NB, and plays an important role in promoting cell growth, proliferation, and invasion in NB, potentially representing a new therapeutic target for tumor progression. Frontiers Media S.A. 2021-12-20 /pmc/articles/PMC8721485/ /pubmed/34988076 http://dx.doi.org/10.3389/fcell.2021.769547 Text en Copyright © 2021 Zhong, Zhang, Zhang, Jiang, Li, Chang, Niu and Shi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhong, Xiaodan
Zhang, Songling
Zhang, Yutong
Jiang, Zongmiao
Li, Yanan
Chang, Jian
Niu, Junqi
Shi, Ying
HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title_full HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title_fullStr HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title_full_unstemmed HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title_short HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2
title_sort hmgb3 is associated with an unfavorable prognosis of neuroblastoma and promotes tumor progression by mediating tpx2
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721485/
https://www.ncbi.nlm.nih.gov/pubmed/34988076
http://dx.doi.org/10.3389/fcell.2021.769547
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