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Long non-coding RNA SNHG7 upregulates FGF9 to alleviate oxygen and glucose deprivation-induced neuron cell injury in a miR-134-5p-dependent manner

Abstract

Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) was reported to regulate the pathogenesis of ischemic stroke. The study aimed to disclose SNHG7 role in oxygen and glucose deprivation (OGD)-induced Neuro-2a (N2a) cell disorders. An OGD injury cell model was established using N2a cells. The expression of SNHG7, microRNA-134-5p (miR-134-5p) and fibroblast growth factor 9 (FGF9) was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by western blot. Cell viability and Lactate Dehydrogenase (LDH) leakage were determined by cell counting kit-8 and LDH activity detection assays. Oxidative stress was investigated by Superoxide Dismutase and Catalase activity assays as well as Malondialdehyde and Reactive Oxygen Species detection kits. Cell apoptosis and caspase-3 activity were severally demonstrated by flow cytometry and caspase-3 activity assays. The interaction between miR-134-5p and SNHG7 or FGF9 was predicted by online databases, and identified by mechanism assays. OGD treatment decreased SNHG7 and FGF9 expression, but increased miR-134-5p expression. OGD treatment repressed cell viability, promoted LDH leakage and induced oxidative stress and apoptosis in N2a cells, which was rescued by SNHG7 overexpression. SNHG7 acted as a sponge for miR-134-5p, and regulated OGD-triggered cell damage by associating with miR-134-5p. Additionally, miR-134-5p depletion protected N2a cells from OGD-induced injury by targeting FGF9. Ectopic SNHG7 expression protected against OGD-induced neuronal cell injury by inducing FGF9 through sponging miR-134-5p, providing a novel therapeutic target for ischemic stroke.

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References

  1. Akella A, Bhattarai S, Dharap A (2019) Long noncoding RNAs in the pathophysiology of ischemic stroke. NeuroMolecular Med 21(4):474–483

    CAS  Article  Google Scholar 

  2. Azhar M, Zeng G, Ahmed A et al (2021) Carnosic acid ameliorates depressive-like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion-induced Sprague Dawley rats. Phytother Res 35(1):384–391

    CAS  Article  Google Scholar 

  3. Bai Y, Zhang Y, Han B et al (2018) Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity. J Neurosci 38(1):32–50

    CAS  Article  Google Scholar 

  4. Bao M-H, Szeto V, Yang BB et al (2018a) Long non-coding RNAs in ischemic stroke. Cell Death Dis 9(3):281

    Article  Google Scholar 

  5. Bao MH, Szeto V, Yang BB et al (2018b) Long non-coding RNAs in ischemic stroke. Cell Death Dis 9(3):281

    Article  Google Scholar 

  6. Bian Z, Ji W, Xu B et al (2020) The role of long noncoding RNA SNHG7 in human cancers (review). Mol Clin Oncol 13(5):45

    CAS  Article  Google Scholar 

  7. Chen J, Cui C, Yang X et al (2017) MiR-126 affects brain-heart interaction after cerebral ischemic stroke. Transl Stroke Res 8(4):374–385

    CAS  Article  Google Scholar 

  8. Chen WB, Zhang LX, Zhao YK et al (2020) C/EBPα-mediated transcriptional activation of miR-134-5p entails KPNA3 inhibition and modulates focal hypoxic-ischemic brain damage in neonatal rats. Brain Res Bull 164:350–360

    CAS  Article  Google Scholar 

  9. Chi W, Meng F, Li Y et al (2014) Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B. Brain Res 1592:22–33

    CAS  Article  Google Scholar 

  10. Cohen RI, Chandross KJ (2000) Fibroblast growth factor-9 modulates the expression of myelin related proteins and multiple fibroblast growth factor receptors in developing oligodendrocytes. J Neurosci Res 61(3):273–287

    CAS  Article  Google Scholar 

  11. Cong R, Wang Y, Wang Y et al (2020) Comprehensive analysis of lncRNA expression pattern and lncRNA-miRNA-mRNA network in a rat model with cavernous nerve injury erectile dysfunction. J Sex Med 17(9):1603–1617

    CAS  Article  Google Scholar 

  12. Cui Y, Wang JQ, Shi XH et al (2019) Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation. Eur Rev Med Pharmacol Sci 23(13):5923–5933

    CAS  PubMed  Google Scholar 

  13. Du K, Zhao C, Wang L et al (2019) MiR-191 inhibit angiogenesis after acute ischemic stroke targeting VEZF1. Aging (Albany NY) 11(9):2762–2786

    CAS  Article  Google Scholar 

  14. Gao X-Z, Ma R-H, Zhang Z-X (2020) miR-339 promotes hypoxia-induced neuronal apoptosis and impairs cell viability by targeting FGF9/CACNG2 and mediating MAPK pathway in ischemic stroke. Front Neurol 11:436

    Article  Google Scholar 

  15. George PM, Steinberg GK (2015) Novel stroke therapeutics: unraveling stroke pathophysiology and its impact on clinical treatments. Neuron 87(2):297–309

    CAS  Article  Google Scholar 

  16. Ghasemi T, Khalaj-Kondori M, Hosseinpour Feizi MA et al (2020) lncRNA-miRNA-mRNA interaction network for colorectal cancer; an in silico analysis. Comput Biol Chem 89:107370

    CAS  Article  Google Scholar 

  17. Kopp F (2019) Molecular functions and biological roles of long non-coding RNAs in human physiology and disease. J Gene Med 21(8):e3104

    Article  Google Scholar 

  18. Liang H, Su X, Wu Q et al (2020) LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a. Autophagy 16(6):1077–1091

    CAS  Article  Google Scholar 

  19. Lu TX, Rothenberg ME (2018) MicroRNA. J Allergy Clin Immunol 141(4):1202–1207

    CAS  Article  Google Scholar 

  20. Panzitt K, Tschernatsch MM, Guelly C et al (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132(1):330–342

    CAS  Article  Google Scholar 

  21. Shan Y, Hu J, Lv H et al (2021) miR-221 exerts neuroprotective effects in ischemic stroke by inhibiting the Proinflammatory response. J Stroke Cerebrovasc Dis 30(2):105489

    Article  Google Scholar 

  22. van Kouwenhove M, Kedde M, Agami R (2011) MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 11(9):644–656

    Article  Google Scholar 

  23. Wang C, Wan H, Wang Q et al (2020) Safflor yellow B attenuates ischemic brain injury via downregulation of long noncoding AK046177 and inhibition of MicroRNA-134 expression in rats. Oxidative Med Cell Longev 2020:4586839

    Google Scholar 

  24. Wu Z, Wu P, Zuo X et al (2017) LncRNA-N1LR enhances neuroprotection against ischemic stroke probably by inhibiting p53 phosphorylation. Mol Neurobiol 54(10):7670–7685

    CAS  Article  Google Scholar 

  25. Wu X, Zheng X, Cheng J et al (2020) LncRNA TUG1 regulates proliferation and apoptosis by regulating miR-148b/IGF2 axis in ox-LDL-stimulated VSMC and HUVEC. Life Sci 243:117287

    CAS  Article  Google Scholar 

  26. Xin H, Katakowski M, Wang F et al (2017) MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke 48(3):747–753

    CAS  Article  Google Scholar 

  27. Xu W, Zheng J, Gao L et al (2017) Neuroprotective effects of stem cells in ischemic stroke. Stem Cells Int 2017:4653936

    PubMed  PubMed Central  Google Scholar 

  28. Xu J, Pei Y, Lu J et al (2021) LncRNA SNHG7 alleviates IL-1β-induced osteoarthritis by inhibiting miR-214-5p-mediated PPARGC1B signaling pathways. Int Immunopharmacol 90:107150

    CAS  Article  Google Scholar 

  29. Zhang X, Zhou G (2020) MiR-199a-5p inhibition protects cognitive function of ischemic stroke rats by AKT signaling pathway. Am J Transl Res 12(10):6549–6558

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang X, Zhu XL, Ji BY et al (2019) LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke. J Neuroinflammation 16(1):75

    Article  Google Scholar 

  31. Zhao J, He L, Yin L (2020) lncRNA NEAT1 binds to MiR-339-5p to increase HOXA1 and alleviate ischemic brain damage in neonatal mice. Mol Ther Nucleic Acids 20:117–127

    CAS  Article  Google Scholar 

  32. Zheng J, Tan Q, Chen H et al (2021) lncRNA-SNHG7-003 inhibits the proliferation, migration and invasion of vascular smooth muscle cells by targeting the miR-1306-5p/SIRT7 signaling pathway. Int J Mol Med 47(2):741–750

    CAS  Article  Google Scholar 

  33. Zhou J, Chen L, Chen B et al (2018) Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol 18(1):198

    CAS  Article  Google Scholar 

  34. Zhou T, Wang S, Lu K et al (2020) Long non-coding RNA SNHG7 alleviates oxygen and glucose deprivation/Reoxygenation-induced neuronal injury by modulating miR-9/SIRT1 Axis in PC12 cells: potential role in ischemic stroke. Neuropsychiatr Dis Treat 16:2837–2848

    CAS  Article  Google Scholar 

  35. Zou R, Zhang D, Lv L et al (2019) Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke. J Transl Med 17(1):45

    Article  Google Scholar 

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Contributions

Wei Sun was responsible for drafting the manuscript. Wei Sun and Lu Sun contributed to the analysis and interpretation of data. Wei Sun, Xiaopeng Sun and Shubei Ma contributed in the data collection. All authors read and approved the final manuscript.

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Correspondence to Shubei Ma.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Dalian Third People’s Hospital Affiliated to Dalian Medical University.

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The authors declare that they have no financial conflicts of interest.

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Sun, W., Sun, L., Sun, X. et al. Long non-coding RNA SNHG7 upregulates FGF9 to alleviate oxygen and glucose deprivation-induced neuron cell injury in a miR-134-5p-dependent manner. Metab Brain Dis 36, 2483–2494 (2021). https://doi.org/10.1007/s11011-021-00852-y

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Keywords

  • Ischemic stroke
  • SNHG7
  • miR-134-5p
  • FGF9