Skip to main content
SpringerLink
Log in

OIP5-AS1 Inhibits Oxidative Stress and Inflammation in Ischemic Stroke Through miR-155-5p/IRF2BP2 Axis

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Background: Ischemic stroke is a very dangerous disease with high incidence, fatality and disability rate in human beings. Massive evidence has indicated that oxidative stress and inflammation are intimately correlated with progression of ischemic stroke. Additionally, LncRNAs were reported to be involved in ischemic stroke. Here, we aim to explore the effects and molecular mechanism of lncRNA OIP5-AS1 on oxidative stress and inflammation in ischemic stroke. Methods: HMC3 and SH-SY5Y cells were under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to establish cell models of ischemic stroke. Commercial kits were employed to detect the indicators of oxidative stress including ROS, MDA and SOD. The expression of OIP5-AS1, miR-155-5p and IRF2BP2 mRNA was determined using RT-qPCR. The protein levels of inflammatory factors including TNF-α, IL-1β and IL-6 and IRF2BP2 were assessed by western blot and/or ELISA. Luciferase activity assay was employed to validate their correlations among OIP5-AS1, miR-155-5p and IRF2BP2. Results: In OGD/R-induced HMC3 and SH-SY5Y cells, the expression of OIP5-AS1 and IRF2BP2 was reduced while miR-155-5p was elevated. OGD/R induction promoted oxidative stress and inflammatory response in HMC3 and SH-SY5Y cells, while OIP5-AS1 or IRF2BP2 sufficiency as well as miR-155-5p inhibitor attenuated OGD/R-induced these influences. In addition, IRF2BP2 knockdown abolished the suppressive impacts of OIP5-AS1 overexpression on oxidative stress and inflammatory response in OGD/R-induced HMC3 and SH-SY5Y cells. Mechanistically, OIP5-AS1 enhanced IRF2BP2 expression via sponging miR-155-5p. Conclusion: OIP5-AS1 suppressed oxidative stress and inflammatory response to alleviate cell injury caused by OGD/R induction in HMC3 and SH-SY5Y cells through regulating miR-155-5p/IRF2BP2 axis, which might offer novel targeted molecules for ischemic stroke therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

OGD/R:

oxygen-glucose deprivation/reoxygenation

ROS:

reactive oxygen species

MDA:

malondialdehyde

SOD:

superoxide dismutase

lncRNA:

Long non-coding RNA

IRF2BP2:

Interferon regulatory factor 2 binding protein2

IRF-2:

Interferon regulatory factor-2

IL4:

Interleukin-4

MCAO/R:

middle cerebral artery occlusion/reperfusion

ox-LDL:

oxidative low-density lipoprotein

HFD:

high fat diet

EMEM:

Eagle’s minimum essential medium

FBS:

fetal bovine serum

ELISA:

Enzyme-linked immunosorbent assay

CCK-8:

cell counting kit-8

References

  1. Feske SK (2021) Ischemic stroke. Am J Med 134:1457–1464

    Article  PubMed  Google Scholar 

  2. Phipps MS et al (2020) Management of acute ischemic stroke. BMJ 368:l6983

    Article  PubMed  Google Scholar 

  3. Feigin VL et al (2018) Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016. N Engl J Med 379:2429–2437

    Article  PubMed  PubMed Central  Google Scholar 

  4. Turc G et al (2019) European Stroke Organisation (ESO) - european Society for minimally invasive neurological therapy (ESMINT) guidelines on mechanical thrombectomy in Acute ischemic stroke. J Neurointerv Surg

  5. Baron JC (2018) Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke. Nat Rev Neurol 14:325–337

    Article  CAS  PubMed  Google Scholar 

  6. Kapranov P et al (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488

    Article  CAS  PubMed  Google Scholar 

  7. Bao MH et al (2018) Long non-coding RNAs in ischemic stroke. Cell Death Dis 9:281

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wang SW et al (2018) Non-coding RNA in Acute ischemic stroke: mechanisms, biomarkers and therapeutic targets. Cell Transpl 27:1763–1777

    Article  Google Scholar 

  9. Zhang X et al (2017) Long noncoding RNA Malat1 regulates cerebrovascular pathologies in ischemic stroke. J Neurosci 37:1797–1806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen Z et al (2021) Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis. Mol Med 27:107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen Y et al (2021) Up-regulating lncRNA OIP5-AS1 protects neuron injury against cerebral hypoxia-ischemia induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p. Int Immunopharmacol 92:107339

    Article  CAS  PubMed  Google Scholar 

  12. Niu X et al (2020) lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway. Cell Prolif 53:e12818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sun H et al (2021) Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high Glucose-Induced oxidative stress of cardiomyocytes by Targeting MicroRNA-34a/SIRT1 Axis in Diabetic Cardiomyopathy. Endocr Metab Immune Disord Drug Targets 21:2017–2027

    Article  CAS  PubMed  Google Scholar 

  14. Chen ZJ et al (2020) Glycine improves ischemic stroke through miR-19a-3p/AMPK/GSK-3β/HO-1 pathway. Drug Des Devel Ther 14:2021–2031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Han B et al (2018) Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy 14:1164–1184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang H et al (2020) Plasma endothelial microvesicles and their carrying miRNA-155 serve as biomarkers for ischemic stroke. J Neurosci Res 98:2290–2301

    Article  CAS  PubMed  Google Scholar 

  17. Shi Y et al (2020) MiR-155-5p accelerates cerebral ischemia-reperfusion injury via targeting DUSP14 by regulating NF-κB and MAPKs signaling pathways. Eur Rev Med Pharmacol Sci 24:1408–1419

    CAS  PubMed  Google Scholar 

  18. Ramalho-Oliveira R et al (2019) IRF2BP2: a new player in the regulation of cell homeostasis. J Leukoc Biol 106:717–723

    Article  CAS  PubMed  Google Scholar 

  19. Kim I et al (2019) The IRF2BP2-KLF2 axis regulates osteoclast and osteoblast differentiation. BMB Rep 52:469–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ma YL et al (2018) Suppressing Irf2bp2 expressions accelerates metabolic syndrome-associated brain injury and hepatic dyslipidemia. Biochem Biophys Res Commun 503:1651–1658

    Article  CAS  PubMed  Google Scholar 

  21. Cruz SA et al (2017) Loss of IRF2BP2 in Microglia increases inflammation and functional deficits after focal ischemic brain Injury. Front Cell Neurosci 11:201

    Article  PubMed  PubMed Central  Google Scholar 

  22. Huang Y (2018) The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J Cell Mol Med 22:5768–5775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou RS et al (2019) Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer 19:779

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lu J et al (2020) LncRNA PVT1 regulates ferroptosis through miR-214-mediated TFR1 and p53. Life Sci 260:118305

    Article  CAS  PubMed  Google Scholar 

  25. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chamorro Á et al (2016) Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 15:869–881

    Article  CAS  PubMed  Google Scholar 

  27. Chen H et al (2020) Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: applications for natural product efficacy with omics and systemic biology. Pharmacol Res 158:104877

    Article  CAS  PubMed  Google Scholar 

  28. Kanazawa M et al (2017) Microglia and Monocytes/Macrophages polarization reveal Novel Therapeutic mechanism against Stroke.Int J Mol Sci18

  29. Zhao Y et al (2022) Neuronal injuries in cerebral infarction and ischemic stroke: from mechanisms to treatment (review).Int J Mol Med49

  30. Agholme L et al (2010) An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J Alzheimers Dis 20:1069–1082

    Article  CAS  PubMed  Google Scholar 

  31. Xu H et al (2021) Neuroprotective effect of cajaninstilbene acid against cerebral ischemia and reperfusion damages by activating AMPK/Nrf2 pathway. J Adv Res 34:199–210

    Article  CAS  PubMed  Google Scholar 

  32. Akella A et al (2019) Long noncoding RNAs in the pathophysiology of ischemic stroke. Neuromolecular Med 21:474–483

    Article  CAS  PubMed  Google Scholar 

  33. Stanzione R et al (2020) Pathogenesis of ischemic stroke: role of epigenetic mechanisms. Genes (Basel, p 11

  34. Greither T et al (2020) MiR-155-5p and MiR-203a-3p are prognostic factors in soft tissue sarcoma. Cancers (Basel) 12

  35. Wu M et al (2020) MiR-155-5p promotes oral cancer progression by targeting chromatin remodeling gene ARID2. Biomed Pharmacother 122:109696

    Article  CAS  PubMed  Google Scholar 

  36. Guo P et al (2020) MiR-155-5p plays as a “janus” in the expression of inflammatory cytokines induced by T-2 toxin. Food Chem Toxicol 140:111258

    Article  CAS  PubMed  Google Scholar 

  37. Huang LG et al (2018) Silencing rno-mir-155-5p in rat temporal lobe epilepsy model reduces pathophysiological features and cell apoptosis by activating Sestrin-3. Brain Res 1689:109–122

    Article  CAS  PubMed  Google Scholar 

  38. Jiang K et al (2020) miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression. Oxid Med Cell Longev 2020:5863617

  39. Zhao L et al (2019) Mir-155-5p inhibits the viability of vascular smooth muscle cell via targeting FOS and ZIC3 to promote aneurysm formation. Eur J Pharmacol 853:145–152

    Article  CAS  PubMed  Google Scholar 

  40. Yu G et al (2019) MiR-142a-3p and mir-155-5p reduce methamphetamine-induced inflammation: role of the target protein Peli1. Toxicol Appl Pharmacol 370:145–153

    Article  CAS  PubMed  Google Scholar 

  41. Liu Y et al (2020) miRNA-mRNA network regulation in the skeletal muscle fiber phenotype of chickens revealed by integrated analysis of miRNAome and transcriptome. Sci Rep 10:10619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chen HH et al (2015) IRF2BP2 reduces macrophage inflammation and susceptibility to atherosclerosis. Circ Res 117:671–683

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by Hainan Provincial Cerebrovascular Disease Clinical Medical Center.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College, Central South University, No.43, People’s Avenue, Meilan District, 570208, Haikou, Hainan Province, P.R. China

    Ji-Kun Zhang, You Li, Zheng-Tao Yu, Jun-Wen Jiang, Hong Tang, Guo-Long Tu & Ying Xia

Authors
  1. Ji-Kun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. You Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zheng-Tao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun-Wen Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guo-Long Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ying Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Guarantor of integrity of the entire study: Ying Xia; study concepts: Ji-Kun Zhang; study design: Ji-Kun Zhang; definition of intellectual content: Ying Xia; literature research: Ji-Kun Zhang, You Li; experimental studies: Ji-Kun Zhang, You Li, Zheng-Tao Yu, Jun-Wen Jiang; data acquisition: You Li, Hong Tang; data analysis: Ji-Kun Zhang, Guo-Long Tu; statistical analysis: Ji-Kun Zhang, Jun-Wen Jiang; manuscript preparation: Ji-Kun Zhang; manuscript editing: Ji-Kun Zhang; manuscript review: Ying Xia; All the authors approved for the final version.

Corresponding author

Correspondence to Ying Xia.

Ethics declarations

Conflict of interest

These authors declared no competing interests in this work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, JK., Li, Y., Yu, ZT. et al. OIP5-AS1 Inhibits Oxidative Stress and Inflammation in Ischemic Stroke Through miR-155-5p/IRF2BP2 Axis. Neurochem Res 48, 1382–1394 (2023). https://doi.org/10.1007/s11064-022-03830-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-022-03830-7

Keywords

Search

Navigation