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Long noncoding RNA SNHG1 protects brain microvascular endothelial cells against oxygen–glucose deprivation/reoxygenation-induced injury by sponging miR-298 and upregulating SIK1 expression

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Abstract

Objectives

Growing evidence shows that long non-coding RNAs (lncRNAs) are widely involved in the progression of multiple diseases, including ischemic stroke. The aim of this study was to explore the function and underlying mechanism of lncRNAs small nucleolar RNA host gene 1 (SNHG1) in ischemic stroke.

Results

SNHG1 and salt-induced kinase 1 (SIK1) were upregulated in oxygen–glucose deprivation/reperfusion (OGD/R)-induced bEnd3 cells. SNHG1 downregulation promoted OGD/R-induced injury through decreasing cell proliferation and increasing apoptosis, which was reversed by upregulating SIK1 or downregulating miR-298. Moreover, SIK1 interference had similar functions with SNHG1 knockdown in OGD/R-treated bEnd3 cells. In addition, miR-298 was a direct target of SNHG1 and could specifically bind to SIK1. Furthermore, SNHG1 functioned as a molecular sponge of miR-298 to regulate SIK1 expression.

Conclusion

SNHG1 knockdown enhanced OGD/R-induced injury in bEnd3 cells by regulating miR-298/SIK1 axis, which might provide promising therapeutic target for treatment of ischemic stroke.

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Abbreviations

SNHG1:

Small nucleolar RNA host gene 1

SIK1:

Salt-induced kinase 1

OGD/R:

Oxygen–glucose deprivation/reperfusion

References

  • Ardekani AM, Naeini MM (2010) The role of microRNAs in human diseases. Avicenna J Med Biotechnol 2:161–179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927

    Article  CAS  Google Scholar 

  • Cao B, Wang T, Qu Q, Kang T, Yang Q (2018) Long noncoding RNA SNHG1 promotes neuroinflammation in Parkinson’s disease via regulating miR-7/NLRP3 pathway. Neuroscience 388:118–127

    Article  CAS  Google Scholar 

  • Chen L-L, Carmichael GG (2010) Decoding the function of nuclear long non-coding RNAs. Curr Opin Cell Biol 22:357–364

    Article  CAS  Google Scholar 

  • Chen F, Zhang L, Wang E, Zhang C, Li X (2018) LncRNA GAS5 regulates ischemic stroke as a competing endogenous RNA for miR-137 to regulate the Notch1 signaling pathway. Biochem Biophys Res Commun 496:184–190

    Article  CAS  Google Scholar 

  • Cheng J, Uchida M, Zhang W, Grafe MR, Herson PS, Hurn PD (2011) Role of salt-induced kinase 1 in androgen neuroprotection against cerebral ischemia. J Cereb Blood Flow Metab 31:339–350

    Article  CAS  Google Scholar 

  • Gallo EF, Iadecola C (2011) Balancing life and death in the ischemic brain: SIK and TORC weigh in. Neuron 69:3–6

    Article  CAS  Google Scholar 

  • Guo D, Ma J, Yan L, Li T, Li Z, Han X, Shui S (2017) Down-regulation of Lncrna MALAT1 attenuates neuronal cell death through suppressing Beclin1-dependent autophagy by regulating Mir-30a in cerebral ischemic stroke. Cell Physiol Biochem 43:182–194

    Article  CAS  Google Scholar 

  • Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477:295–300

    Article  CAS  Google Scholar 

  • Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185

    Article  CAS  Google Scholar 

  • Jalali S, Bhartiya D, Lalwani MK, Sivasubbu S, Scaria V (2013) Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PLoS ONE 8:e53823

    Article  CAS  Google Scholar 

  • Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6:590–610

    Article  CAS  Google Scholar 

  • Kumar MS, Armenteros-Monterroso E, East P, Chakravorty P, Matthews N, Winslow MM, Downward J (2014) HMGA2 functions as a competing endogenous RNA to promote lung cancer progression. Nature 505:212

    Article  CAS  Google Scholar 

  • Lai TW, Shyu W-C, Wang YT (2011) Stroke intervention pathways: NMDA receptors and beyond. Trends Mol Med 17:266–275

    Article  CAS  Google Scholar 

  • Madden JA (2012) Role of the vascular endothelium and plaque in acute ischemic stroke. Neurology 79:S58–S62

    Article  CAS  Google Scholar 

  • Mozaffarian D, Benjamin E, Go A, Arnett D, Blaha M, Cushman M, Das S, de Ferranti S, Després J, Fullerton H (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133:e38

    PubMed  Google Scholar 

  • Noorbakhsh J, Lang AH, Mehta P (2013) Intrinsic noise of microRNA-regulated genes and the ceRNA hypothesis. PLoS ONE 8:e72676

    Article  CAS  Google Scholar 

  • Ouyang Y-B, Giffard RG (2012) ER-mitochondria crosstalk during cerebral ischemia: molecular chaperones and ER-mitochondrial calcium transfer. Int J Cell Biol 2012:493934

    Article  Google Scholar 

  • Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146:353–358

    Article  CAS  Google Scholar 

  • Sandoval KE, Witt KA (2008) Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiol Dis 32:200–219

    Article  CAS  Google Scholar 

  • Sun H, Zhong D, Wang C, Sun Y, Zhao J, Li G (2018) MiR-298 exacerbates ischemia/reperfusion injury following ischemic stroke by targeting Act1. Cell Physiol Biochem 48:528–539

    Article  CAS  Google Scholar 

  • Wang L, Niu Y, He G, Wang J (2019) Down-regulation of lncRNA GAS5 attenuates neuronal cell injury through regulating miR-9/FOXO3 axis in cerebral ischemic stroke. RSC advances 9:16158–16166

    Article  CAS  Google Scholar 

  • Wu Z, Wu P, Zuo X, Yu N, Qin Y, Xu Q, He S, Cen B, Liao W, Ji A (2017) LncRNA-N1LR enhances neuroprotection against ischemic stroke probably by inhibiting p53 phosphorylation. Mol Neurobiol 54:7670–7685

    Article  CAS  Google Scholar 

  • Yang X, Zi X-H (2019) LncRNA SNHG1 alleviates OGD induced injury in BMEC via miR-338/HIF-1α axis. Brain Res 1714:174–181

    Article  CAS  Google Scholar 

  • Yao X, Yao R, Huang F, Yi J (2019) LncRNA SNHG12 as a potent autophagy inducer exerts neuroprotective effects against cerebral ischemia/reperfusion injury. Biochem Biophys Res Commun 514:490–496

    Article  CAS  Google Scholar 

  • Yue Y-H, Bai X-d, Zhang H-j, Li Y-m, Hu L, Liu L-y, Mao J-p, Yang X-y, Dila N-m (2016) Gene polymorphisms affect the effectiveness of atorvastatin in treating ischemic stroke patients. Cell Physiol Biochem 39:630–638

    Article  CAS  Google Scholar 

  • Zhang M, Wang W, Li T, Yu X, Zhu Y, Ding F, Li D, Yang T (2016) Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis. Biomed Pharmacother 80:73–79

    Article  CAS  Google Scholar 

  • Zhang G, Sun H, Zhang Y, Zhao H, Fan W, Li J, Lv Y, Song Q, Li J, Zhang M (2018a) Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction. Cell Death Discov 4:1–13

    Google Scholar 

  • Zhang L, Luo X, Chen F, Yuan W, Xiao X, Zhang X, Dong Y, Zhang Y, Liu Y (2018b) LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF-1α/VEGF signaling in ischemic stroke. J Cell Biochem 119:5460–5472

    Article  CAS  Google Scholar 

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Acknowledgement

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Supporting information

Supplementary Fig. 1 MiR-298 expression was decreased in OGD/R-induced bEnd3. The expression of miR-298 was measured by qRT-PCR in bEnd3 cells after treatment with OGD/R for 0 h, 6 h, 12 h, 24 h, or 48 h. *P< 0.05.

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Author notes

  1. Xinyu Zhou and Bingchao Xu authors contributed equally to this work.

Authors and Affiliations

  1. The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China

    Xinyu Zhou, Bingchao Xu & Yan Gu

  2. The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, China

    Niu Ji & Pin Meng

  3. Department of Pathology, Maternal and Child Health Hospital of Hubei Province, No. 745, Wu Luo Road, Hongshan District, Wuhan, 430070, Hubei province, China

    Lingdan Dong

Authors
  1. Xinyu Zhou
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  2. Bingchao Xu
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  3. Yan Gu
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  4. Niu Ji
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  5. Pin Meng
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  6. Lingdan Dong
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Correspondence to Lingdan Dong.

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Zhou, X., Xu, B., Gu, Y. et al. Long noncoding RNA SNHG1 protects brain microvascular endothelial cells against oxygen–glucose deprivation/reoxygenation-induced injury by sponging miR-298 and upregulating SIK1 expression. Biotechnol Lett 43, 1163–1174 (2021). https://doi.org/10.1007/s10529-021-03096-z

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  • DOI: https://doi.org/10.1007/s10529-021-03096-z

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