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13-05-2023 | Stroke | Original Article

miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation

Authors: Shengnan Li, Peiyi Zhu, Yajun Wang, Shaoting Huang, Zhaochun Wu, Jiawen He, Xingjuan Hu, Ying Wang, Yanquan Yuan, Bin Zhao, Guoda Ma, You Li

Published in: Metabolic Brain Disease | Issue 6/2023

Abstract

Evidence suggests that the microRNA-181 (miR-181) family performs various roles in the pathophysiology of cerebral ischemia and reperfusion injury (CIRI). MiR-181a has been identified as a critical determinant of neuronal survival. Moreover, the significance of miR-181a in controlling neuronal death after CIRI has received little attention. The objective of this study was to assess the role of miR-181a in neuronal cell injury after CIRI. To mimic the in-vitro and in-vivo CIRI, we developed an oxygen-glucose deficiency/reoxygenation (OGD/R) model in SH-SY5Y cells and a transient middle cerebral artery occlusion model in rats. MiR-181a expression was significantly higher in both in-vivo and in-vitro CIRI models. The overexpression of miR-181a increased cell damage and oxidative stress caused by OGD/R, whereas inhibition of miR-181a reduced both. PTEN has also been found to be a direct miR-181a target. PTEN overexpression reduced cell apoptosis and oxidative stress induced by miR-181a upregulation under an OGD/R condition. Furthermore, we found that the rs322931 A allele was related to increased miR-181a levels in IS peripheral blood and higher susceptibility to IS. The current results offer new insights into the understanding of the molecular pathophysiology of CIRI, as well as possible new treatment candidates.

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Cuartero MI, de la Parra J, Garcia-Culebras A, Ballesteros I, Lizasoain I, Moro MA (2016) The kynurenine pathway in the acute and chronic phases of cerebral ischemia. Curr Pharm Des 22:1060–1073. http://doi.org/CTMC-EPUB-62482

Ghafouri-Fard S, Abak A, Shoorei H, Mohaqiq M, Majidpoor J, Sayad A, Taheri M (2021) Regulatory role of microRNAs on PTEN signaling. Biomed Pharmacother 133:110986. http://doi.org/S0753-3322(20)31178-1

Guo XL, Liang H, Sun Y, Wang CB (2019) MicroRNA-26a regulates cerebral ischemia injury through targeting PTEN. Eur Rev Med Pharmacol Sci 23:7033–7041. http://doi.org/S0753-3322(20)31178-1

Han X, Zheng Z, Wang C, Wang L (2018) Association between MEG3/miR-181b polymorphisms and risk of ischemic stroke. Lipids Health Dis 17. https://doi.org/10.1186/s12944-018-0941-z

Huang SY, Sung CS, Chen WF, Chen CH, Feng CW, Yang SN, Hung HC, Chen NF, Lin PR, Chen SC, Wang HM, Chu TH, Tai MH, Wen ZH (2015) Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain. J Neuroinflamm 12:59. https://doi.org/10.1186/s12974-015-0280-1CrossRef

Jean WC, Spellman SR, Nussbaum ES, Low WC (1998) Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery 43:1382–1396, discussion 1396–1387. https://doi.org/10.1097/00006123-199812000-00076

Lancaster TM, Ihssen N, Brindley LM, Linden DE (2017) Further support for association between GWAS variant for positive emotion and reward systems. Transl Psychiatry 7:e1018. https://doi.org/10.1038/tp.2016.289CrossRefPubMedPubMedCentral

Li HY, He HC, Song JF, Du YF, Guan M, Wu CY (2020) Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-beta1 signaling. Cell Signal 66:109436. http://doi.org/S0898-6568(19)30232-3

Li L, Cui P, Ge H, Shi Y, Wu X, Fan Ru Z (2020b) miR-188-5p inhibits apoptosis of neuronal cells during oxygen-glucose deprivation (OGD)-induced stroke by suppressing PTEN. Exp Mol Pathol 116:104512. http://doi.org/S0014-4800(20)30788-7

Li S, Wang Y, Wang M, Chen L, Chen S, Deng F, Zhu P, Hu W, Chen X, Zhao B, Ma G, Li Y (2021) microRNA-186 alleviates oxygen-glucose deprivation/reoxygenation-induced injury by directly targeting hypoxia-inducible factor-1alpha. J Biochem Mol Toxicol 35:1–11. https://doi.org/10.1002/jbt.22752CrossRefPubMed

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262CrossRefPubMed

Lv X, Li Y, Gong Q, Jiang Z (2019) TGF-beta1 induces airway smooth muscle cell proliferation and remodeling in asthmatic mice by up-regulating miR-181a and suppressing PTEN. Int J Clin Exp Pathol 12:173–181PubMedPubMedCentral

Moskowitz MA, Lo EH, Iadecola C (2010) The science of stroke: mechanisms in search of treatments. Neuron 67:181–198. https://doi.org/10.1016/j.neuron.2010.07.002CrossRefPubMedPubMedCentral

Mu J, Cheng X, Zhong S, Chen X, Zhao C (2020) Neuroprotective effects of mir-532-5p against ischemic stroke. Metab Brain Dis 35:753–763. https://doi.org/10.1007/s11011-020-00544-zCrossRefPubMed

Ouyang YB, Lu Y, Yue S, Xu LJ, Xiong XX, White RE, Sun X, Giffard RG (2012) miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. Neurobiol Dis 45:555–563. https://doi.org/10.1016/j.nbd.2011.09.012CrossRefPubMed

Pan R, Xie Y, Fang W, Liu Y, Zhang Y (2022) USP20 mitigates ischemic stroke in mice by suppressing neuroinflammation and neuron death via regulating PTEN signal. Int Immunopharmacol 103:107840. http://doi.org/S1567-5769(21)00476-8

Saba R, Storchel PH, Aksoy-Aksel A, Kepura F, Lippi G, Plant TD, Schratt GM (2012) Dopamine-regulated microRNA MiR-181a controls GluA2 surface expression in hippocampal neurons. Mol Cell Biol 32:619–632. https://doi.org/10.1128/MCB.05896-11CrossRefPubMedPubMedCentral

Shabanzadeh AP, D’Onofrio PM, Magharious M, Choi KAB, Monnier PP, Koeberle PD (2019) Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury. Cell Death Dis 10:567. https://doi.org/10.1038/s41419-019-1802-zCrossRefPubMedPubMedCentral

Song MS, Salmena L, Pandolfi PP (2012) The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 13:283–296. https://doi.org/10.1038/nrm3330CrossRefPubMed

Song J, He Q, Guo X, Wang L, Wang J, Cui C, Hu H, Yang M, Cui Y, Zang N, Yan F, Liu F, Sun Y, Liang K, Qin J, Zhao R, Wang C, Sun Z, Hou X, Li W, Chen L (2021) Mesenchymal stem cell-conditioned medium alleviates high fat-induced hyperglucagonemia via miR-181a-5p and its target PTEN/AKT signaling. Mol Cell Endocrinol 537:111445. http://doi.org/S0303-7207(21)00289-6

Sun C, Chen C, Chen Z, Guo J, Yu ZH, Qian W, Ai F, Xiao L, Guo X (2022) MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway. Anal Cell Pathol (Amst) 2022. https://doi.org/10.1155/2022/3421600

Wingo AP, Almli LM, Stevens JS, Jovanovic T, Wingo TS, Tharp G, Li Y, Lori A, Briscione M, Jin P, Binder EB, Bradley B, Gibson G, Ressler KJ (2017) Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs. Mol Psychiatry 22:774–783. https://doi.org/10.1038/mp.2016.143CrossRefPubMed

Xu LJ, Ouyang YB, Xiong X, Stary CM, Giffard RG (2015) Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Exp Neurol 264:1–7. https://doi.org/10.1016/j.expneurol.2014.11.007CrossRefPubMed

Yi Z, Shi Y, Zhao P, Xu Y, Pan P (2020) Overexpression of mir-217-5p protects against oxygen-glucose deprivation/reperfusion-induced neuronal injury via inhibition of PTEN. Hum Cell 33:1026–1035. https://doi.org/10.1007/s13577-020-00396-wCrossRefPubMed

Zhang Y, Shan Z, Zhao Y, Ai Y (2019) Sevoflurane prevents miR-181a-induced cerebral ischemia/reperfusion injury. Chem Biol Interact 308:332–338. http://doi.org/S0009-2797(19)30429-6

Zhao J, Yin L, Jiang L, Hou L, He L, Zhang C (2021) PTEN nuclear translocation enhances neuronal injury after hypoxia-ischemia via modulation of the nuclear factor-kappab signaling pathway. Aging 13:16165–16177. https://doi.org/10.18632/aging.203141CrossRefPubMedPubMedCentral

Zheng T, Shi Y, Zhang J, Peng J, Zhang X, Chen K, Chen Y, Liu L (2019) MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway. Biomed Pharmacother 117:109117. http://doi.org/S0753-3322(19)31505-7

Title: miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation
Authors: Shengnan Li
Peiyi Zhu
Yajun Wang
Shaoting Huang
Zhaochun Wu
Jiawen He
Xingjuan Hu
Ying Wang
Yanquan Yuan
Bin Zhao
Guoda Ma
You Li
Publication date: 13-05-2023
Publisher: Springer US
Keyword: Stroke
Published in: Metabolic Brain Disease / Issue 6/2023
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01219-1

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Springer Medicine

miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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