Cargando…

HK3 stimulates immune cell infiltration to promote glioma deterioration

BACKGROUND: Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Shupeng, Li, Ziwei, Wang, Xinyu, Zhong, Junzhe, Yu, Daohan, Chen, Hao, Ma, Wenbin, Liu, Lingling, Ye, Minghuang, Shen, Ruofei, Jiang, Chuanlu, Meng, Xiangqi, Cai, Jinquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543879/
https://www.ncbi.nlm.nih.gov/pubmed/37779195
http://dx.doi.org/10.1186/s12935-023-03039-w
_version_ 1785114380287868928
author Li, Shupeng
Li, Ziwei
Wang, Xinyu
Zhong, Junzhe
Yu, Daohan
Chen, Hao
Ma, Wenbin
Liu, Lingling
Ye, Minghuang
Shen, Ruofei
Jiang, Chuanlu
Meng, Xiangqi
Cai, Jinquan
author_facet Li, Shupeng
Li, Ziwei
Wang, Xinyu
Zhong, Junzhe
Yu, Daohan
Chen, Hao
Ma, Wenbin
Liu, Lingling
Ye, Minghuang
Shen, Ruofei
Jiang, Chuanlu
Meng, Xiangqi
Cai, Jinquan
author_sort Li, Shupeng
collection PubMed
description BACKGROUND: Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions between neoplastic cells and the surrounding microenvironment can generate an immunosuppressive TME, which can accelerate the malignant progression of glioma. Therefore, it is crucial to explore associations between energy metabolism and the immunosuppressive TME and to identify new biomarkers for glioma prognosis. METHODS: In our work, we analyzed the co-expression relationship between glycolytic genes and immune checkpoints based on the transcriptomic data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) and found the correlation between HK3 expression and glioma tumor immune status. To investigate the biological role of HK3 in glioma, we performed bioinformatics analysis and established a mouse glioblastoma (GBM) xenograft model. RESULTS: Our study showed that HK3 significantly stimulated immune cell infiltration into the glioma TME. Tissue samples with higher HK3 expressive level showed increasing levels of immune cells infiltration, including M2 macrophages, neutrophils, and various subtypes of activated memory CD4(+) T cells. Furthermore, HK3 expression was significantly increasing along with the elevated tumor grade, had a higher level in the mesenchymal subtype compared with those in other subtypes of GBM and could independently predict poor outcomes of GBM patients. CONCLUSION: The present work mainly concentrated on the biological role of HK3 in glioma and offered a novel insight of HK3 regulating the activation of immune cells in the glioma microenvironment. These findings could provide a new theoretical evidence for understanding the metabolic molecular within the glioma microenvironment and identifying new therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03039-w.
format Online
Article
Text
id pubmed-10543879
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-105438792023-10-03 HK3 stimulates immune cell infiltration to promote glioma deterioration Li, Shupeng Li, Ziwei Wang, Xinyu Zhong, Junzhe Yu, Daohan Chen, Hao Ma, Wenbin Liu, Lingling Ye, Minghuang Shen, Ruofei Jiang, Chuanlu Meng, Xiangqi Cai, Jinquan Cancer Cell Int Research BACKGROUND: Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions between neoplastic cells and the surrounding microenvironment can generate an immunosuppressive TME, which can accelerate the malignant progression of glioma. Therefore, it is crucial to explore associations between energy metabolism and the immunosuppressive TME and to identify new biomarkers for glioma prognosis. METHODS: In our work, we analyzed the co-expression relationship between glycolytic genes and immune checkpoints based on the transcriptomic data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) and found the correlation between HK3 expression and glioma tumor immune status. To investigate the biological role of HK3 in glioma, we performed bioinformatics analysis and established a mouse glioblastoma (GBM) xenograft model. RESULTS: Our study showed that HK3 significantly stimulated immune cell infiltration into the glioma TME. Tissue samples with higher HK3 expressive level showed increasing levels of immune cells infiltration, including M2 macrophages, neutrophils, and various subtypes of activated memory CD4(+) T cells. Furthermore, HK3 expression was significantly increasing along with the elevated tumor grade, had a higher level in the mesenchymal subtype compared with those in other subtypes of GBM and could independently predict poor outcomes of GBM patients. CONCLUSION: The present work mainly concentrated on the biological role of HK3 in glioma and offered a novel insight of HK3 regulating the activation of immune cells in the glioma microenvironment. These findings could provide a new theoretical evidence for understanding the metabolic molecular within the glioma microenvironment and identifying new therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03039-w. BioMed Central 2023-10-01 /pmc/articles/PMC10543879/ /pubmed/37779195 http://dx.doi.org/10.1186/s12935-023-03039-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Shupeng
Li, Ziwei
Wang, Xinyu
Zhong, Junzhe
Yu, Daohan
Chen, Hao
Ma, Wenbin
Liu, Lingling
Ye, Minghuang
Shen, Ruofei
Jiang, Chuanlu
Meng, Xiangqi
Cai, Jinquan
HK3 stimulates immune cell infiltration to promote glioma deterioration
title HK3 stimulates immune cell infiltration to promote glioma deterioration
title_full HK3 stimulates immune cell infiltration to promote glioma deterioration
title_fullStr HK3 stimulates immune cell infiltration to promote glioma deterioration
title_full_unstemmed HK3 stimulates immune cell infiltration to promote glioma deterioration
title_short HK3 stimulates immune cell infiltration to promote glioma deterioration
title_sort hk3 stimulates immune cell infiltration to promote glioma deterioration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543879/
https://www.ncbi.nlm.nih.gov/pubmed/37779195
http://dx.doi.org/10.1186/s12935-023-03039-w
work_keys_str_mv AT lishupeng hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT liziwei hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT wangxinyu hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT zhongjunzhe hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT yudaohan hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT chenhao hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT mawenbin hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT liulingling hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT yeminghuang hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT shenruofei hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT jiangchuanlu hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT mengxiangqi hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration
AT caijinquan hk3stimulatesimmunecellinfiltrationtopromotegliomadeterioration