It has been reported that microRNAs (miRNAs) play essential roles in cerebral ischemia and reperfusion (I/R) injury. This study aimed to explore the role of miR-361-5p in oxygen–glucose deprivation/re-oxygenation-induced neuronal injury in vitro. Cerebral I/R injury cell model was established by using PC12 cells exposed to oxygen–glucose deprivation/re-oxygenation (OGD/R). The expression of miR-361-5p and SQSTM1 was evaluated by qRT-PCR or western blot. Neuronal apoptosis was detected by flow cytometry, and cell viability was assessed by CCK-8 assay. The effects of miR-361-5p on the release of LDH and the levels of MDA, SOD, and GSH-Px were investigated by respective detection kits. Dual-luciferase reporter assay and RIP assay were performed to determine the interaction between miR-361-5p and SQSTM1. Rescue experiments were performed to evaluate the function of miR-361-5p and SQSTM1. MiR-361-5p was significantly upregulated, and SQSTM1 was significantly downregulated in OGD/R-stimulated PC12 cells. MiR-361-5p could directly interact with SQSTM1 and negatively regulated it. Inhibition of miR-361-5p efficiently inhibited OGD/R-induced apoptosis and attenuated OGD/R-induced growth defect in PC12 cells. In addition, SQSTM1 overexpression partially attenuates the apoptosis and promoted the viability of OGD/R-treated PC12 cells, which were aggravated by miR-361-5p mimics. Our study demonstrated that miR-361-5p promotes OGD/R-induced neuronal injury via regulating SQSTM1 in PC12 cells.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
The data are not publicly available due to their containing information that could compromise the privacy of research participants, but are available on request from the corresponding author.
Bai M, Pan CL, Jiang GX, Zhang YM, Zhang Z (2019) CircHIPK3 aggravates myocardial ischemia-reperfusion injury by binding to miRNA-124-3p. Eur Rev Med Pharmacol Sci 23:10107–10114. https://doi.org/10.26355/eurrev_201911_19580
Chai Z, Gong J, Zheng P, Zheng J (2020) Inhibition of miR-19a-3p decreases cerebral ischemia/reperfusion injury by targeting IGFBP3 in vivo and in vitro. Biol Res 53:17. https://doi.org/10.1186/s40659-020-00280-9
Chitnis T, Weiner HL (2017) CNS inflammation and neurodegeneration. J Clin Investig 127:3577–3587. https://doi.org/10.1172/jci90609
Galkin A (2019) Brain ischemia/reperfusion injury and mitochondrial complex I damage biochemistry. Biokhimiia 84:1411–1423. https://doi.org/10.1134/S0006297919110154
Ghafouri-Fard S, Bahroudi Z, Shoorei H, Abak A, Ahin M, Taheri M (2021) microRNA-140: a miRNA with diverse roles in human diseases. Biomed Pharmacother 135:111256. https://doi.org/10.1016/j.biopha.2021.111256
Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150. https://doi.org/10.1042/bst0351147
Hammond SM (2015) An overview of microRNAs. Adv Drug Deliv Rev 87:3–14. https://doi.org/10.1016/j.addr.2015.05.001
Hankey GJ (2017) Stroke. Lancet 389:641–654. https://doi.org/10.1016/S0140-6736(16)30962-X
Hao C, Chen S (2021) Knockdown of lncRNA TTTY15 alleviates ischemia/reperfusion-induced inflammation and apoptosis of PC12 cells by targeting miR-766-5p. Exp Therapeut Med 21:511. https://doi.org/10.3892/etm.2021.9942
Hao Y, Xin M, Feng L, Wang X, Wang X, Ma D, Feng J (2020) Review cerebral ischemic tolerance and preconditioning: methods, mechanisms, clinical applications, and challenges. Front Neurol 11:812. https://doi.org/10.3389/fneur.2020.00812
He Q, Li Z, Wang Y, Hou Y, Li L, Zhao J (2017) Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction. Int Immunopharmacol 50:208–215. https://doi.org/10.1016/j.intimp.2017.06.029
Hemond CC et al (2019) MRI phenotypes in MS: Longitudinal changes and miRNA signatures. Neurology Neuroimmunol Neuroinflamm 6:e530. https://doi.org/10.1212/nxi.0000000000000530
Jiang C, Dong N, Feng J, Hao M (2021) MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway. Pflug Archiv 473:121–130. https://doi.org/10.1007/s00424-020-02490-2
Liang Y et al (2018) Inhibition of MiRNA-125b decreases cerebral ischemia/reperfusion injury by targeting CK2α/NADPH oxidase signaling. Cell Physiol Biochem 45:1818–1826. https://doi.org/10.1159/000487873
Long N et al (2020) CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells. Cancer Cell Int 20:374. https://doi.org/10.1186/s12935-020-01454-x
Lu TX, Rothenberg ME (2018) MicroRNA. J Allergy Clin Immunol 141:1202–1207. https://doi.org/10.1016/j.jaci.2017.08.034
Lu WX (2019) Long non-coding RNA MEG3 represses cholangiocarcinoma by regulating miR-361-5p/TRAF3 axis. Eur Rev Med Pharmacol Sci 23:7356–7368. https://doi.org/10.26355/eurrev_201909_18842
Ma M, Zhang J, Gao X, Yao W, Li Q (2020) miR-361-5p mediates SMAD4 to promote porcine granulosa cell apoptosis through VEGFA. Biomolecules. https://doi.org/10.3390/biom10091281
Mandalaneni K, Rayi A, Jillella DV (2020) Stroke reperfusion injury. In: StatPearls. StatPearls, Treasure Island
Mao L, Zuo ML, Hu GH, Duan XM, Yang ZB (2017) mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury. Oncotarget 8:99681–99692. https://doi.org/10.18632/oncotarget.21129
Mao L et al (2020) Low expression of miR-532-3p contributes to cerebral ischemia/reperfusion oxidative stress injury by directly targeting NOX2. Mol Med Rep 22:2415–2423. https://doi.org/10.3892/mmr.2020.11325
Mohr AM, Mott JL (2015) Overview of microRNA biology. Semin Liver Dis 35:3–11. https://doi.org/10.1055/s-0034-1397344
Ren Z, Xie P, Lv J, Hu Y, Guan Z, Chen L, Yu W (2020) miR-187-3p inhibitor attenuates cerebral ischemia/reperfusion injury by regulating Seipin-mediated autophagic flux. Int J Mol Med 46:1051–1062. https://doi.org/10.3892/ijmm.2020.4642
Roth GA et al (2020) Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am College Cardiol 76:2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010
Sun H, Li JJ, Feng ZR, Liu HY, Meng AG (2020) MicroRNA-124 regulates cell pyroptosis during cerebral ischemia-reperfusion injury by regulating STAT3. Exp Therapeut Med 20:227. https://doi.org/10.3892/etm.2020.9357
Sun K, Fan J, Han J (2015) Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage. Acta Pharm Sin B 5:8–24. https://doi.org/10.1016/j.apsb.2014.11.002
Sun X, Li X, Ma S, Guo Y, Li Y (2018) MicroRNA-98–5p ameliorates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by inhibiting Bach1 and promoting Nrf2/ARE signaling. Biochem Biophys Res Commun 507:114–121. https://doi.org/10.1016/j.bbrc.2018.10.182
Wang A, Hu N, Zhang Y, Chen Y, Su C, Lv Y, Shen Y (2019) MEG3 promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-361–5p/FOXO1 axis. BMC Med Genom 12:201. https://doi.org/10.1186/s12920-019-0649-6
Wang P, Shao BZ, Deng Z, Chen S, Yue Z, Miao CY (2018) Autophagy in ischemic stroke. Prog Neurobiol 163–164:98–117. https://doi.org/10.1016/j.pneurobio.2018.01.001
Wu Y, Yao J, Feng K (2020) miR-124–5p/NOX2 axis modulates the ROS production and the inflammatory microenvironment to protect against the cerebral I/R injury. Neurochem Res 45:404–417. https://doi.org/10.1007/s11064-019-02931-0
Yang CC et al (2020) Down-regulating microRNA-20a regulates CDH1 to protect against cerebral ischemia/reperfusion injury in rats. Cell Cycle. https://doi.org/10.1080/15384101.2020.1856498
Yang W, Xie T (2020) Hsa_circ_CSPP1/MiR-361–5p/ITGB1 regulates proliferation and migration of cervical cancer (CC) by modulating the PI3K-Akt signaling pathway. Reprod Sci 27:132–144. https://doi.org/10.1007/s43032-019-00008-5
Yang X, Song Y, Sun Y, Wang M, Xiang Y (2020) Down-regulation of miR-361-5p promotes the viability, migration and tube formation of endothelial progenitor cells via targeting FGF1. Biosci Rep. https://doi.org/10.1042/bsr20200557
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-w
Yin LC, Xiao G (2020) MicroRNA-361-5p inhibits tumorigenesis and the EMT of HCC by targeting twist1. Biomed Res Int 2020:8891876. https://doi.org/10.1155/2020/8891876
Zhou L et al (2021) MicroRNA-488-3p regulates neuronal cell death in cerebral ischemic stroke through vacuolar protein sorting 4B (VPS4B). Neuropsych Dis Treatm 17:41–55. https://doi.org/10.2147/ndt.s255666
Zhu H, Fan GC (2012) Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. Cardiovasc Res 94:284–292. https://doi.org/10.1093/cvr/cvr291
We thank Science and Technology Project of Guangdong Province for approving.
This work was supported by the Science and Technology Project of Guangdong Province (2018KJYZ026).
Conflict of interest
All authors declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.
Consent to participate
Consent to publish
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Zeng, T., Zhang, S., He, Y. et al. MiR-361-5p promotes oxygen–glucose deprivation/re-oxygenation induced neuronal injury by negatively regulating SQSTM1 in vitro. Metab Brain Dis 36, 2359–2368 (2021). https://doi.org/10.1007/s11011-021-00845-x
- Oxygen–glucose deprivation/re-oxygenation