Abstract
To investigate the role of miR-372/Beclin-1 on nerve cell apoptosis induced by spinal cord ischemia/reperfusion injury (SCII). We established in vivo and in vitro SCII model. MiR-372 and Beclin-1 expressions in spinal cord tissues of SCII rats and SCII nerve cells were measured. The cell apoptosis was detected by flow cytometry. MiR-372 inhibitor was used to reduce miR-372 expression. Dual luciferase reporter assay was used to confirm the interaction between miR-372 and Beclin-1. MiR-372 expression in spinal cord tissues of SCII rats and SCII nerve cells was increased, while Beclin-1 expression was decreased. Knockdown of miR-372 could inhibit SCII nerve cell apoptosis. In addition, MiR-372 could negatively regulate Beclin-1 expression. Autophagy inhibitor could inhibit autophagy to promote the apoptosis of SCII nerve cells through decreasing Beclin-1, while interference of miR-372 changed the effect of autophagy inhibitor. Interference of miR-372 could reduce nerve cell apoptosis in SCII via increasing autophagy by up-regulating Beclin-1.
Similar content being viewed by others
References
Baba H, Sakurai M, Abe K, Tominaga R (2009) Autophagy-mediated stress response in motor neuron after transient ischemia in rabbits. J Vasc Surg 50:381–387. https://doi.org/10.1016/j.jvs.2009.03.042
Chang CJ, Lin JF, Hsiao CY, Chang HH, Li HJ, Chang HH, Lee GA, Hung CF (2017a) Lutein induces autophagy via Beclin-1 upregulation in IEC-6 rat intestinal epithelial cells. Am J Chin Med 45:1273–1291. https://doi.org/10.1142/s0192415x17500707
Chang Z, Zhong Y, Jia Y (2017b) The role of microRNAs in the occurrence and development of esophageal squamous cell carcinoma. Clin Surg Res Commun 1:1–9
Chen H, Zhang Z, Lu Y, Song K, Liu X, Xia F, Sun W (2017) Downregulation of ULK1 by microRNA-372 inhibits the survival of human pancreatic adenocarcinoma cells. Cancer Sci 108:1811–1819. https://doi.org/10.1111/cas.13315
Cheng X, Chen J, Huang Z (2018) miR-372 promotes breast cancer cell proliferation by directly targeting LATS2. Exp Ther Med 15:2812–2817. https://doi.org/10.3892/etm.2018.5761
Divac Rankov A, Ljujic M, Petric M, Radojkovic D, Pesic M, Dinic J (2017) Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells. Histochem Cell Biol 148:529–544. https://doi.org/10.1007/s00418-017-1590-4
Fan J, Zhang Z, Chao X, Gu J, Cai W, Zhou W, Yin G, Li Q (2014) Ischemic preconditioning enhances autophagy but suppresses autophagic cell death in rat spinal neurons following ischemia-reperfusion. Brain Res 1562:76–86. https://doi.org/10.1016/j.brainres.2014.03.019
Fang B, Qin M, Li Y, Li X, Tan W, Zhang Y, Ma H (2017) Electroacupuncture preconditioning and postconditioning inhibit apoptosis and neuroinflammation induced by spinal cord ischemia reperfusion injury through enhancing autophagy in rats. Neurosci Lett 642:136–141. https://doi.org/10.1016/j.neulet.2017.02.010
Ge WQ, Hao P, Huang YH, Hou JQ, Pu JX, Wang LL (2018) miR-539 inhibits inflammation in renal transplant iscemia-reperfusion injury via blocking the MyD88/NF-κB pathway. Clin Surg Res Commun 2:14–21
Glover K, Li Y, Mukhopadhyay S, Leuthner Z, Chakravarthy S, Colbert CL (2017) Structural transitions in conserved, ordered Beclin 1 domains essential to regulating autophagy. J Biol Chem 292:16235–16248. https://doi.org/10.1074/jbc.M117.804195
Gokce EC et al (2016) Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis. J Neurosurg Spine 24:949–959. https://doi.org/10.3171/2015.10.spine15612
Li L, Jiang HK, Li YP, Guo YP (2015) Hydrogen sulfide protects spinal cord and induces autophagy via miR-30c in a rat model of spinal cord ischemia-reperfusion injury. J Biomed Sci 22:50. https://doi.org/10.1186/s12929-015-0135-1
Li S, Zhang J, Wang Z, Wang T, Yu Y, He J, Zhang H, Yang T, Shen Z (2016) MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression. Liver Transpl 22:1697–1709. https://doi.org/10.1002/lt.24606
Liu B, Huang W, Xiao X, Xu Y, Ma S, Xia Z (2015) Neuroprotective effect of ulinastatin on spinal cord ischemia-reperfusion injury in rabbits. Oxidative Med Cell Longev 2015:624819. https://doi.org/10.1155/2015/624819
Maejima Y, Isobe M, Sadoshima J (2016) Regulation of autophagy by Beclin 1 in the heart. J Mol Cell Cardiol 95:19–25. https://doi.org/10.1016/j.yjmcc.2015.10.032
Valente G, Morani F (2014) Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. Biomed Res Int 2014:462658. https://doi.org/10.1155/2014/462658
Wang ZY, Lin JH, Muharram A, Liu WG (2014) Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis. Apoptosis 19:933–945. https://doi.org/10.1007/s10495-014-0976-1
Wang Q, Liu S, Zhao X, Wang Y, Tian D, Jiang W (2017) MiR-372-3p promotes cell growth and metastasis by targeting FGF9 in lung squamous cell carcinoma. Cancer Med 6:1323–1330. https://doi.org/10.1002/cam4.1026
Wang P et al (2018a) AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats CNS. Neurosci Ther. https://doi.org/10.1111/cns.12856
Wang Y, Pang QJ, Liu JT, Wu HH, Tao DY (2018b) Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1. Braz J Med Biol Res 51:e7319. https://doi.org/10.1590/1414-431x20177319
Zhao D, Deng SC, Ma Y, Hao YH, Jia ZH (2018) miR-221 alleviates the inflammatory response and cell apoptosis of neuronal cell through targeting TNFAIP2 in spinal cord ischemia-reperfusion. Neuroreport 29:655–660. https://doi.org/10.1097/wnr.0000000000001013
Zhou W, Yuan T, Gao Y, Yin P, Liu W, Pan C, Liu Y, Yu X (2017) IL-1beta-induces NF-kappaB and upregulates microRNA-372 to inhibit spinal cord injury recovery. J Neurophysiol 117:2282–2291. https://doi.org/10.1152/jn.00936.2016
Funding
This study was supported by the Natural Science Foundation of China (No. 81401004 and No. 81402862).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, X., Lou, X., Xu, S. et al. Knockdown of miR-372 Inhibits Nerve Cell Apoptosis Induced by Spinal Cord Ischemia/Reperfusion Injury via Enhancing Autophagy by Up-regulating Beclin-1. J Mol Neurosci 66, 437–444 (2018). https://doi.org/10.1007/s12031-018-1179-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-018-1179-y