MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma

IntroductionAn effective therapeutic method to noticeably improve the prognosis of glioma patients has not been developed thus far. MAPK-activated protein kinase 2 (MAPKAPK2) is a serine/threonine kinase, which is involved in tumorigenesis, tumor growth, metastasis, and the inflammatory process. The...

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Main Authors: Jinmin Sun, Sicheng Wu, Wenyu Zhao, Senrui Xue, Lei Zhang, Jing Ren
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1307992/full
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author Jinmin Sun
Jinmin Sun
Sicheng Wu
Wenyu Zhao
Wenyu Zhao
Senrui Xue
Lei Zhang
Jing Ren
author_facet Jinmin Sun
Jinmin Sun
Sicheng Wu
Wenyu Zhao
Wenyu Zhao
Senrui Xue
Lei Zhang
Jing Ren
author_sort Jinmin Sun
collection DOAJ
description IntroductionAn effective therapeutic method to noticeably improve the prognosis of glioma patients has not been developed thus far. MAPK-activated protein kinase 2 (MAPKAPK2) is a serine/threonine kinase, which is involved in tumorigenesis, tumor growth, metastasis, and the inflammatory process. The clinical significance and molecular function of MAPKAPK2 in glioma remain unclear.MethodsMAPKAPK2 expression in human glioma tissues was detected by immunohistochemistry and analyzed from the transcriptome sequencing data in TCGA and CGGA. Prognostic nomogram was constructed to predict the survival risk of individual patients. GO and KEGG enrichment analyses were performed to analyze the function and pathways MAPKAPK2 involved. Single-cell RNA sequencing data was used to analyze the cell types in which MAPKAPK2 was enriched. Flow cytometry was used for cell cycle and apoptosis detection. The ability of cell proliferation and migration was analyzed by CCK8 and cell migration assay, respectively. Correlation analyses were performed to analyze the relationship of MAPKAPK2 with immune infiltration, immune regulators, chemokine, and chemokine receptors.ResultsMAPKAPK2 was not only aberrantly upregulated in glioma tissues but also correlated with poor clinical characteristics. Moreover, MAPKAPK2 was prevalent in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion glioma cohorts and predicted poor prognosis of glioma patients. MAPKAPK2 may be involved in cell proliferation, cell migration, DNA damage repair, and immune regulation in glioma. MAPKAPK2 was enriched in microglia/macrophages and malignant tumor cells. Further investigation into cellular function revealed that inhibiting MAPKAPK2 suppressed the proliferation and migration of glioblastoma multiforme (GBM) cells in vitro. The inhibition of MAPKAPK2 significantly induced the G1 cell cycle arrest and cell apoptosis of GBM cells. Consistent with the enriched function of MAPKAPK2 in immune regulation, MAPKAPK2 was correlated with immune cell infiltration in glioma tissues. Mechanistically, a series of immune regulators, immunomodulatory chemokine, and chemokine receptors were positively correlated with MAPKAPK2 expression.DiscussionOur findings provide evidence of the clinical relevance of MAPKAPK2 in prognosis evaluation of glioma patients and highlight the underlying significance of MAPKAPK2 in glioma therapy.
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spelling doaj.art-1664a05141094137baa70699ba4a90832024-01-23T04:44:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-01-011410.3389/fonc.2024.13079921307992MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in gliomaJinmin Sun0Jinmin Sun1Sicheng Wu2Wenyu Zhao3Wenyu Zhao4Senrui Xue5Lei Zhang6Jing Ren7Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaLaboratory of Clinical and Experimental Pathology, Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaJiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaJiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaLaboratory of Clinical and Experimental Pathology, Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaJiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaJiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaIntroductionAn effective therapeutic method to noticeably improve the prognosis of glioma patients has not been developed thus far. MAPK-activated protein kinase 2 (MAPKAPK2) is a serine/threonine kinase, which is involved in tumorigenesis, tumor growth, metastasis, and the inflammatory process. The clinical significance and molecular function of MAPKAPK2 in glioma remain unclear.MethodsMAPKAPK2 expression in human glioma tissues was detected by immunohistochemistry and analyzed from the transcriptome sequencing data in TCGA and CGGA. Prognostic nomogram was constructed to predict the survival risk of individual patients. GO and KEGG enrichment analyses were performed to analyze the function and pathways MAPKAPK2 involved. Single-cell RNA sequencing data was used to analyze the cell types in which MAPKAPK2 was enriched. Flow cytometry was used for cell cycle and apoptosis detection. The ability of cell proliferation and migration was analyzed by CCK8 and cell migration assay, respectively. Correlation analyses were performed to analyze the relationship of MAPKAPK2 with immune infiltration, immune regulators, chemokine, and chemokine receptors.ResultsMAPKAPK2 was not only aberrantly upregulated in glioma tissues but also correlated with poor clinical characteristics. Moreover, MAPKAPK2 was prevalent in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion glioma cohorts and predicted poor prognosis of glioma patients. MAPKAPK2 may be involved in cell proliferation, cell migration, DNA damage repair, and immune regulation in glioma. MAPKAPK2 was enriched in microglia/macrophages and malignant tumor cells. Further investigation into cellular function revealed that inhibiting MAPKAPK2 suppressed the proliferation and migration of glioblastoma multiforme (GBM) cells in vitro. The inhibition of MAPKAPK2 significantly induced the G1 cell cycle arrest and cell apoptosis of GBM cells. Consistent with the enriched function of MAPKAPK2 in immune regulation, MAPKAPK2 was correlated with immune cell infiltration in glioma tissues. Mechanistically, a series of immune regulators, immunomodulatory chemokine, and chemokine receptors were positively correlated with MAPKAPK2 expression.DiscussionOur findings provide evidence of the clinical relevance of MAPKAPK2 in prognosis evaluation of glioma patients and highlight the underlying significance of MAPKAPK2 in glioma therapy.https://www.frontiersin.org/articles/10.3389/fonc.2024.1307992/fullgliomaMAPKAPK2prognosisproliferationmigration
spellingShingle Jinmin Sun
Jinmin Sun
Sicheng Wu
Wenyu Zhao
Wenyu Zhao
Senrui Xue
Lei Zhang
Jing Ren
MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
Frontiers in Oncology
glioma
MAPKAPK2
prognosis
proliferation
migration
title MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
title_full MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
title_fullStr MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
title_full_unstemmed MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
title_short MAPK-activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
title_sort mapk activated protein kinase 2 is associated with poor prognosis of glioma patients and immune inhibition in glioma
topic glioma
MAPKAPK2
prognosis
proliferation
migration
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1307992/full
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