PMID- 35927233 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220808 IS - 2058-7716 (Print) IS - 2058-7716 (Electronic) IS - 2058-7716 (Linking) VI - 8 IP - 1 DP - 2022 Aug 4 TI - Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma. PG - 349 LID - 10.1038/s41420-022-01136-9 [doi] LID - 349 AB - 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. CI - (c) 2022. The Author(s). FAU - Long, Niya AU - Long N AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. FAU - Xu, Xu AU - Xu X AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. AD - School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China. FAU - Lin, Hongyi AU - Lin H AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. AD - School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China. FAU - Lv, Ying AU - Lv Y AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. FAU - Zou, Shenghui AU - Zou S AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. FAU - Cao, Han AU - Cao H AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. FAU - Chen, Xueshu AU - Chen X AD - Department of Clinical Laboratory, Guizhou Cancer Hospital, Guiyang, Guizhou, China. FAU - Zhao, Yan AU - Zhao Y AD - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou, China. FAU - Qi, Xiaolan AU - Qi X AD - School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China. AD - Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou, China. FAU - Yang, Hua AU - Yang H AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. FAU - Liu, Jian AU - Liu J AD - Department of Neurosurgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China. FAU - Chu, Liangzhao AU - Chu L AUID- ORCID: 0000-0002-1861-2473 AD - Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China. chulz_gmu@163.com. AD - School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China. chulz_gmu@163.com. LA - eng PT - Journal Article DEP - 20220804 PL - United States TA - Cell Death Discov JT - Cell death discovery JID - 101665035 PMC - PMC9352789 COIS- The authors declare no competing interests. EDAT- 2022/08/05 06:00 MHDA- 2022/08/05 06:01 PMCR- 2022/08/04 CRDT- 2022/08/04 23:15 PHST- 2021/11/08 00:00 [received] PHST- 2022/07/18 00:00 [accepted] PHST- 2022/07/13 00:00 [revised] PHST- 2022/08/04 23:15 [entrez] PHST- 2022/08/05 06:00 [pubmed] PHST- 2022/08/05 06:01 [medline] PHST- 2022/08/04 00:00 [pmc-release] AID - 10.1038/s41420-022-01136-9 [pii] AID - 1136 [pii] AID - 10.1038/s41420-022-01136-9 [doi] PST - epublish SO - Cell Death Discov. 2022 Aug 4;8(1):349. doi: 10.1038/s41420-022-01136-9.