PMID- 34739656 OWN - NLM STAT- MEDLINE DCOM- 20220520 LR - 20220531 IS - 1567-2387 (Electronic) IS - 1567-2379 (Linking) VI - 53 IP - 2 DP - 2022 Apr TI - CircDLGAP4 overexpression relieves oxygen-glucose deprivation-induced neuronal injury by elevating NEGR1 through sponging miR-503-3p. PG - 321-332 LID - 10.1007/s10735-021-10036-8 [doi] AB - Circular RNAs (circRNAs) have been reported to play vital regulatory roles in human diseases. However, the functions of circRNAs in ischemic stroke (IS) are limited. In this study, we aimed to explore the functions and mechanisms of circRNA DLG associated protein 4 (circDLGAP4) in IS development. Oxygen-glucose deprivation (OGD)-treated HCN-2 cells were used to mimic IS environment in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect the levels of circDLGAP4, microRNA-503-3p (miR-503-3p) and neuronal growth regulator 1 (NEGR1) mRNA. RNase R assay was conducted to analyze the stability of circDLGAP4. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were adopted for cell viability and death, respectively. Western blot assay was performed for protein levels. Enzyme-linked immunosorbent assay (ELISA) kits were used to examine the concentrations of inflammatory cytokines. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were employed to analyze the relationships among circDLGAP4, miR-503-3p and NEGR1. CircDLGAP4 level was declined in HCN-2 cells after OGD treatment. CircDLGAP4 overexpression promoted cell viability and suppressed cell death and inflammatory cytokine concentrations in OGD-treated HCN-2 cells. CircDLGAP4 acted as the sponge for miR-503-3p and the impacts of circDLGAP4 overexpression on cell viability, death and inflammation in OGD-treated HCN-2 cells were reversed by miR-503-3p elevation. Furthermore, NEGR1 was the target gene of miR-503-3p. MiR-503-3p inhibition ameliorated OGD-induced HCN-2 cell impairments, but NEGR1 knockdown abolished the effects. CircDLGAP4 alleviated OGD-induced HCN-2 cell damage by regulating miR-503-3p/NEGR1 axis. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Qiu, Lingling AU - Qiu L AD - Department of Neurology, Taizhou Municipal Hospital, No.381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China. FAU - He, Jinfeng AU - He J AD - Department of Neurology, Taizhou Municipal Hospital, No.381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China. FAU - Chen, Hui AU - Chen H AD - Department of Neurology, Taizhou Municipal Hospital, No.381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China. FAU - Xu, Xiaohui AU - Xu X AD - Department of Neurology, Taizhou Municipal Hospital, No.381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China. FAU - Tao, Yongjun AU - Tao Y AD - Department of Neurology, Taizhou Municipal Hospital, No.381 Zhongshan East Road, Jiaojiang District, Taizhou, 318000, Zhejiang Province, China. taoyongjun19910121@163.com. LA - eng GR - No.1701KY39/Taizhou Bureau of Science and Technology/ GR - No. 2019KY783/Health Science and Technology Project of Zhejiang Province/ PT - Journal Article DEP - 20211105 PL - Netherlands TA - J Mol Histol JT - Journal of molecular histology JID - 101193653 RN - 0 (Cell Adhesion Molecules, Neuronal) RN - 0 (DLGAP4 protein, human) RN - 0 (GPI-Linked Proteins) RN - 0 (MIRN503 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NEGR1 protein, human) RN - 0 (RNA, Circular) RN - 0 (SAP90-PSD95 Associated Proteins) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - *Cell Adhesion Molecules, Neuronal/metabolism MH - *GPI-Linked Proteins/metabolism MH - Glucose/metabolism MH - Humans MH - *MicroRNAs/genetics/metabolism MH - Neurons/metabolism MH - Oxygen/metabolism MH - *RNA, Circular/genetics MH - SAP90-PSD95 Associated Proteins OTO - NOTNLM OT - IS OT - NEGR1 OT - OGD OT - circDLGAP4 OT - miR-503-3p EDAT- 2021/11/06 06:00 MHDA- 2022/05/21 06:00 CRDT- 2021/11/05 17:26 PHST- 2021/06/02 00:00 [received] PHST- 2021/10/28 00:00 [accepted] PHST- 2021/11/06 06:00 [pubmed] PHST- 2022/05/21 06:00 [medline] PHST- 2021/11/05 17:26 [entrez] AID - 10.1007/s10735-021-10036-8 [pii] AID - 10.1007/s10735-021-10036-8 [doi] PST - ppublish SO - J Mol Histol. 2022 Apr;53(2):321-332. doi: 10.1007/s10735-021-10036-8. Epub 2021 Nov 5.