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RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway

Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data wer...

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Autores principales: Liu, Baoling, Su, Quanping, Xiao, Bolian, Zheng, Guodong, Zhang, Lizhong, Yin, Jiawei, Wang, Lijuan, Che, Fengyuan, Heng, Xueyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666624/
https://www.ncbi.nlm.nih.gov/pubmed/34912698
http://dx.doi.org/10.3389/fonc.2021.657029
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author Liu, Baoling
Su, Quanping
Xiao, Bolian
Zheng, Guodong
Zhang, Lizhong
Yin, Jiawei
Wang, Lijuan
Che, Fengyuan
Heng, Xueyuan
author_facet Liu, Baoling
Su, Quanping
Xiao, Bolian
Zheng, Guodong
Zhang, Lizhong
Yin, Jiawei
Wang, Lijuan
Che, Fengyuan
Heng, Xueyuan
author_sort Liu, Baoling
collection PubMed
description Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways.
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spelling pubmed-86666242021-12-14 RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway Liu, Baoling Su, Quanping Xiao, Bolian Zheng, Guodong Zhang, Lizhong Yin, Jiawei Wang, Lijuan Che, Fengyuan Heng, Xueyuan Front Oncol Oncology Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways. Frontiers Media S.A. 2021-11-29 /pmc/articles/PMC8666624/ /pubmed/34912698 http://dx.doi.org/10.3389/fonc.2021.657029 Text en Copyright © 2021 Liu, Su, Xiao, Zheng, Zhang, Yin, Wang, Che and Heng 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
Liu, Baoling
Su, Quanping
Xiao, Bolian
Zheng, Guodong
Zhang, Lizhong
Yin, Jiawei
Wang, Lijuan
Che, Fengyuan
Heng, Xueyuan
RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_full RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_fullStr RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_full_unstemmed RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_short RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_sort rab42 promotes glioma pathogenesis via the vegf signaling pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666624/
https://www.ncbi.nlm.nih.gov/pubmed/34912698
http://dx.doi.org/10.3389/fonc.2021.657029
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