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:	Baoling Liu, Quanping Su, Bolian Xiao, Guodong Zheng, Lizhong Zhang, Jiawei Yin, Lijuan Wang, Fengyuan Che, Xueyuan Heng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glioma RAB42 vascular endothelial growth factor (VEGF) tumorigenesis CGGA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/044ed47a58f94e8eb54af33e2e2b20dd
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spelling	oai:doaj.org-article:044ed47a58f94e8eb54af33e2e2b20dd2021-12-01T12:46:07ZRAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway2234-943X10.3389/fonc.2021.657029https://doaj.org/article/044ed47a58f94e8eb54af33e2e2b20dd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.657029/fullhttps://doaj.org/toc/2234-943XAngiogenesis 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.Baoling LiuQuanping SuBolian XiaoGuodong ZhengLizhong ZhangJiawei YinLijuan WangLijuan WangFengyuan CheFengyuan CheXueyuan HengFrontiers Media S.A.articlegliomaRAB42vascular endothelial growth factor (VEGF)tumorigenesisCGGANeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioma RAB42 vascular endothelial growth factor (VEGF) tumorigenesis CGGA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glioma RAB42 vascular endothelial growth factor (VEGF) tumorigenesis CGGA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Baoling Liu Quanping Su Bolian Xiao Guodong Zheng Lizhong Zhang Jiawei Yin Lijuan Wang Lijuan Wang Fengyuan Che Fengyuan Che Xueyuan Heng RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
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.
format	article
author	Baoling Liu Quanping Su Bolian Xiao Guodong Zheng Lizhong Zhang Jiawei Yin Lijuan Wang Lijuan Wang Fengyuan Che Fengyuan Che Xueyuan Heng
author_facet	Baoling Liu Quanping Su Bolian Xiao Guodong Zheng Lizhong Zhang Jiawei Yin Lijuan Wang Lijuan Wang Fengyuan Che Fengyuan Che Xueyuan Heng
author_sort	Baoling Liu
title	RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway
title_short	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_sort	rab42 promotes glioma pathogenesis via the vegf signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/044ed47a58f94e8eb54af33e2e2b20dd
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RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway

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