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LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway

BACKGROUND: LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined. METHODS: In this s...

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Autores principales: Gao, Lei, Wu, Jia, Wang, Hai, Yang, Yongyu, Zheng, Zongliao, Ni, Bowen, Wang, Xiran, Peng, Yuping, Li, Yaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907846/
https://www.ncbi.nlm.nih.gov/pubmed/35280742
http://dx.doi.org/10.3389/fonc.2022.770299
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author Gao, Lei
Wu, Jia
Wang, Hai
Yang, Yongyu
Zheng, Zongliao
Ni, Bowen
Wang, Xiran
Peng, Yuping
Li, Yaomin
author_facet Gao, Lei
Wu, Jia
Wang, Hai
Yang, Yongyu
Zheng, Zongliao
Ni, Bowen
Wang, Xiran
Peng, Yuping
Li, Yaomin
author_sort Gao, Lei
collection PubMed
description BACKGROUND: LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined. METHODS: In this study, expression level data and clinical information were obtained via three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. In vitro and in vivo assays were used to explore the function of LMO1 in human glioma. Gene set enrichment analysis (GSEA), RNA-seq and western blot were used to explore the potential molecular mechanisms. A prognostic model was built for predicting the overall survival(OS) of human glioma patients. RESULTS: High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. High levels of LMO1 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) and 1p/19q non-codeletion gliomas. Gene silencing of LMO1 significantly inhibited tumor growth, invasion and migration in vitro. In contrast, LMO1 over-expression promoted tumor growth, invasion and migration. Mechanically, LMO1 may positively regulate the level of NGFR mRNA and protein. NGFR mediated the regulation between LMO1 and NF-kB activation. Consistently, the nude mice study further confirmed that knockdown of LMO1 blocked tumor growth via NGFR-NF-kB axis. Finally, The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk. CONCLUSION: This study provides new insights and evidences that high level expression of LMO1 is significantly correlated with progression and prognosis in human gliomas. LMO1 played a critical role in tumorigenesis and progression. The present study first investigated the LMO1–NGFR–NF-kB axis regulate cell growth and invasion in human glioma cells, whereby targeting this pathway may be a therapeutic target for glioma.
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spelling pubmed-89078462022-03-11 LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway Gao, Lei Wu, Jia Wang, Hai Yang, Yongyu Zheng, Zongliao Ni, Bowen Wang, Xiran Peng, Yuping Li, Yaomin Front Oncol Oncology BACKGROUND: LIM domain only protein1(LMO1), a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the clinical significance and potential mechanism of LMO1 in human gliomas remain to be determined. METHODS: In this study, expression level data and clinical information were obtained via three databases. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. In vitro and in vivo assays were used to explore the function of LMO1 in human glioma. Gene set enrichment analysis (GSEA), RNA-seq and western blot were used to explore the potential molecular mechanisms. A prognostic model was built for predicting the overall survival(OS) of human glioma patients. RESULTS: High LMO1 expression was associated with a high tumor grade and a poor prognosis in patients. High levels of LMO1 mRNA were correlated with poor prognosis in patients with isocitrate dehydrogenase (IDH)-wild-type (wt) and 1p/19q non-codeletion gliomas. Gene silencing of LMO1 significantly inhibited tumor growth, invasion and migration in vitro. In contrast, LMO1 over-expression promoted tumor growth, invasion and migration. Mechanically, LMO1 may positively regulate the level of NGFR mRNA and protein. NGFR mediated the regulation between LMO1 and NF-kB activation. Consistently, the nude mice study further confirmed that knockdown of LMO1 blocked tumor growth via NGFR-NF-kB axis. Finally, The nomogram based on the LMO1 signature for overall survival (OS) prediction in human glioma patients exhibited good performance in the individual mortality risk. CONCLUSION: This study provides new insights and evidences that high level expression of LMO1 is significantly correlated with progression and prognosis in human gliomas. LMO1 played a critical role in tumorigenesis and progression. The present study first investigated the LMO1–NGFR–NF-kB axis regulate cell growth and invasion in human glioma cells, whereby targeting this pathway may be a therapeutic target for glioma. Frontiers Media S.A. 2022-02-24 /pmc/articles/PMC8907846/ /pubmed/35280742 http://dx.doi.org/10.3389/fonc.2022.770299 Text en Copyright © 2022 Gao, Wu, Wang, Yang, Zheng, Ni, Wang, Peng and Li 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 Oncology
Gao, Lei
Wu, Jia
Wang, Hai
Yang, Yongyu
Zheng, Zongliao
Ni, Bowen
Wang, Xiran
Peng, Yuping
Li, Yaomin
LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title_full LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title_fullStr LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title_full_unstemmed LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title_short LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway
title_sort lmo1 plays an oncogenic role in human glioma associated with nf-kb pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907846/
https://www.ncbi.nlm.nih.gov/pubmed/35280742
http://dx.doi.org/10.3389/fonc.2022.770299
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