circCELF1 Induces the Apoptosis and Autophagy of Astrocytes in Ischemic Stroke via Upregulating NFAT5

Li W. · Teng J.

Author affiliations

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing Of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Original Paper

Received: December 30, 2021
Accepted: July 28, 2022
Published online: September 19, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 1

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: https://www.karger.com/CED

Abstract

Introduction: Ischemic stroke, an abrupt blockage of artery, accounting for the most cases of stroke, causes high neurological mortality across the world. Recent evidence has uncovered that circular RNAs (circRNAs) highly engage in ischemic stroke-related neuronal injury. This study concentrated on a novel circRNA hsa_circ_0000304 (termed as circCELF1), trying to unveil its role and underlying mechanism in ischemic stroke. Methods: RT-qPCR and Western blot assays were conducted to detect the expression levels of RNA and protein, respectively. Functional analysis was performed to evaluate the influences of circCELF1 expression on astrocyte apoptosis and autophagy. Multiple mechanism assays were performed to probe the molecular mechanism underlying circCELF1 regulation. The oxygen-glucose deprivation/reoxygenation (OGD/R)-induced astrocytes model and transient middle cerebral artery occlusion (tMCAO) mouse model were constructed. Results: circCELF1 was found to be upregulated in OGD/R-induced astrocytes, relative to normal astrocytes. circCELF1 knockdown repressed the apoptosis and autophagy of astrocytes. The in vivo study conducted with the tMCAO model also revealed that circCELF1 or NFAT5 deficiency contributed to the suppression of neural injury. Further, circCELF1 was uncovered to elevate NFAT5 expression via recruiting DDX54, functionally promoting astrocyte apoptosis and autophagy. Conclusion: circCELF1 recruits DDX54 to upregulate NFAT5, by which astrocyte apoptosis and autophagy are stimulated.

© 2022 S. Karger AG, Basel

References Paul S, Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: an overview of clinical and preclinical studies. Exp Neurol. 2021;335:113518. Maida CD, Norrito RL, Daidone M, Tuttolomondo A, Pinto A. Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci. 2020;21(18):E6454. Boese AC, Lee JP, Hamblin MH. Neurovascular protection by peroxisome proliferator-activated receptor α in ischemic stroke. Exp Neurol. 2020;331:113323. Datta A, Sarmah D, Mounica L, Kaur H, Kesharwani R, Verma G, et al. Cell death pathways in ischemic stroke and targeted pharmacotherapy. Transl Stroke Res. 2020;11(6):1185–202. Yang L, Han B, Zhang Z, Wang S, Bai Y, Zhang Y, et al. Extracellular vesicle-mediated delivery of circular RNA SCMH1 promotes functional recovery in rodent and nonhuman primate ischemic stroke models. Circulation. 2020;142(6):556–74. Chen W, Wang H, Zhu Z, Feng J, Chen L. Exosome-shuttled circSHOC2 from IPASs regulates neuronal autophagy and ameliorates ischemic brain injury via the miR-7670-3p/SIRT1 axis. Mol Ther Nucleic Acids. 2020;22:657–72. Bai Y, Zhang Y, Han B, Yang L, Chen X, Huang R, et al. Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity. J Neurosci. 2018;38(1):32–50. Chen W, Wang H, Feng J, Chen L. Overexpression of circRNA circUCK2 attenuates cell apoptosis in cerebral ischemia-reperfusion injury via miR-125b-5p/GDF11 signaling. Mol Ther Nucleic Acids. 2020;22:673–83. Chang KT, Wang LH, Lin YM, Cheng CF, Wang GS. CELF1 promotes vascular endothelial growth factor degradation resulting in impaired microvasculature in heart failure. FASEB J. 2021;35(5):e21512. Wang H, Liu G, Li T, Wang N, Wu J, Zhi H. MiR-330-3p functions as a tumor suppressor that regulates glioma cell proliferation and migration by targeting CELF1. Arch Med Sci. 2020;16(5):1166–75. Gu L, Wang H, Wang J, Guo Y, Tang Y, Mao Y, et al. Reconstitution of HuR-inhibited CUGBP1 expression protects cardiomyocytes from acute myocardial infarction-induced injury. Antioxid Redox Signal. 2017;27(14):1013–26. Wang Z, Lei X. Matrix factorization with neural network for predicting circRNA-RBP interactions. BMC Bioinformatics. 2020;21(1):229. Liang Y, Wang H, Chen B, Mao Q, Xia W, Zhang T, et al. circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression. Mol Ther Nucleic Acids. 2021;23:355–68. Han B, Zhang Y, Zhang Y, Bai Y, Chen X, Huang R, et al. Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy. 2018;14(7):1164–84. Lin SP, Ye S, Long Y, Fan Y, Mao HF, Chen MT, et al. Circular RNA expression alterations are involved in OGD/R-induced neuron injury. Biochem Biophys Res Commun. 2016;471(1):52–6. Wang H, Zheng X, Jin J, Zheng L, Guan T, Huo Y, et al. LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4. J Biomed Sci. 2020;27(1):40. Zhao SC, Wang C, Xu H, Wu WQ, Chu ZH, Ma LS, et al. Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice. Acta Pharmacol Sin. 2017;38(11):1425–34. Chen X, Li M, Li L, Xu S, Huang D, Ju M, et al. Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Sci Rep. 2016;6:28423. Wang H, Huang R, Guo W, Qin X, Yang Z, Yuan Z, et al. RNA-binding protein CELF1 enhances cell migration, invasion, and chemoresistance by targeting ETS2 in colorectal cancer. Clin Sci. 2020;134(14):1973–90. Wu F, Han B, Wu S, Yang L, Leng S, Li M, et al. Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP. J Neurosci. 2019;39(37):7369–93. Peng L, Sang H, Wei S, Li Y, Jin D, Zhu X, et al. circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2. Mol Cancer. 2020;19(1):156. Duan S, Wang F, Cao J, Wang C. Exosomes derived from MicroRNA-146a-5p-enriched bone marrow mesenchymal stem cells alleviate intracerebral hemorrhage by inhibiting neuronal apoptosis and microglial M1 polarization. Drug Des Devel Ther. 2020;14:3143–58. Guo Q, Wu Y, Guo X, Cao L, Xu F, Zhao H, et al. The RNA-binding protein CELF2 inhibits ovarian cancer progression by stabilizing FAM198B. Mol Ther Nucleic acids. 2021;23:169–84. Su XT, Wang L, Ma SM, Cao Y, Yang NN, Lin LL, et al. Mechanisms of acupuncture in the regulation of oxidative stress in treating ischemic stroke. Oxid Med Cell Longev. 2020;2020:7875396. Akella A, Bhattarai S, Dharap A. Long noncoding RNAs in the pathophysiology of ischemic stroke. Neuromolecular Med. 2019;21(4):474–83. Bai Y, Zhang Y, Han B, Yang L, Chen X, Huang R, et al. Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity. J Neurosci. 2018;38(1):32–50. Shaterian A, Borboa A, Coimbra R, Baird A, Eliceiri BP. Non-invasive detection of spatio-temporal activation of SBE and NFAT5 promoters in transgenic reporter mice following stroke. Neuropathology. 2012;32(2):118–23. O’Sullivan MP, Casey S, Finder M, Ahearne C, Clarke G, Hallberg B, et al. Up-regulation of Nfat5 mRNA and Fzd4 mRNA as a marker of poor outcome in neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2021;228:74–81.e2. Zang J, Lu D, Xu A. The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function. J Neurosci Res. 2020;98(1):87–97. Kahl A, Blanco I, Jackman K, Baskar J, Mohan HM, Rodney-Sandy R, et al. Publisher correction: cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases. Sci Rep. 2018;8(1):6802. Yu Y, Wang JL, Meng LL, Hu CT, Yan ZW, He ZP, et al. DDX54 plays a cancerous role through activating P65 and AKT signaling pathway in colorectal cancer. Front Oncol. 2021;11:650360. Liu B, Yao P, Xiao F, Guo J, Wu L, Yang Y. MYBL2-induced PITPNA-AS1 upregulates SIK2 to exert oncogenic function in triple-negative breast cancer through miR-520d-5p and DDX54. J Transl Med. 2021;19(1):333. Article / Publication Details

First-Page Preview

Abstract of Original Paper

Received: December 30, 2021
Accepted: July 28, 2022
Published online: September 19, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 1

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: https://www.karger.com/CED

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif