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Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma

Glioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated...

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Autores principales: Long, Niya, Xu, Xu, Lin, Hongyi, Lv, Ying, Zou, Shenghui, Cao, Han, Chen, Xueshu, Zhao, Yan, Qi, Xiaolan, Yang, Hua, Liu, Jian, Chu, Liangzhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352789/
https://www.ncbi.nlm.nih.gov/pubmed/35927233
http://dx.doi.org/10.1038/s41420-022-01136-9
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author Long, Niya
Xu, Xu
Lin, Hongyi
Lv, Ying
Zou, Shenghui
Cao, Han
Chen, Xueshu
Zhao, Yan
Qi, Xiaolan
Yang, Hua
Liu, Jian
Chu, Liangzhao
author_facet Long, Niya
Xu, Xu
Lin, Hongyi
Lv, Ying
Zou, Shenghui
Cao, Han
Chen, Xueshu
Zhao, Yan
Qi, Xiaolan
Yang, Hua
Liu, Jian
Chu, Liangzhao
author_sort Long, Niya
collection PubMed
description Glioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy.
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spelling pubmed-93527892022-08-06 Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma Long, Niya Xu, Xu Lin, Hongyi Lv, Ying Zou, Shenghui Cao, Han Chen, Xueshu Zhao, Yan Qi, Xiaolan Yang, Hua Liu, Jian Chu, Liangzhao Cell Death Discov Article Glioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy. Nature Publishing Group UK 2022-08-04 /pmc/articles/PMC9352789/ /pubmed/35927233 http://dx.doi.org/10.1038/s41420-022-01136-9 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Long, Niya
Xu, Xu
Lin, Hongyi
Lv, Ying
Zou, Shenghui
Cao, Han
Chen, Xueshu
Zhao, Yan
Qi, Xiaolan
Yang, Hua
Liu, Jian
Chu, Liangzhao
Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title_full Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title_fullStr Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title_full_unstemmed Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title_short Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma
title_sort circular rna circpostn promotes neovascularization by regulating mir-219a-2-3p/stc1 axis and stimulating the secretion of vegfa in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352789/
https://www.ncbi.nlm.nih.gov/pubmed/35927233
http://dx.doi.org/10.1038/s41420-022-01136-9
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