Abstract：Objective To determine the association of circular RNA (circRNA) and circRNA-microRNA (miRNA) network regulation with brain injury induced by inflammation in preterm mice. Methods Pregnant mice were treated with intraperitoneally injected lipopolysaccharide to establish a preterm mouse model of brain injury induced by inflammation (inflammation preterm group with 3 mice). Preterm mice born to normal pregnant mice by cesarean section were selected as controls (non-inflammation preterm group with 3 mice). The gene microarray technique was used to screen out the circRNAs associated with brain injury in preterm mice. The miRNA target prediction software was used to predict the binding sites between circRNAs and miRNAs and analyze the regulatory mechanism. Results A total of 365 differentially expressed circRNAs were screened out between the inflammation preterm and non-inflammation preterm groups (fold change > 1.5, P < 0.05), among which there were 206 upregulated circRNAs and 159 downregulated circRNAs. Further analysis of the circRNAs with a fold change of > 4 showed that these circRNAs could bind to miRNAs and regulate their activity, thereby regulating the expression of the genes associated with the nervous system. Conclusions Inflammation induces a significant change in the expression profile of circRNAs in the brain tissue of mice, and the change in the expression of circRNAs plays an important role in brain injury induced by inflammation and subsequent brain development in preterm mice.
WEI Si-Meng,XIAO Mi,ZHENG Xi et al. Role and mechanism of circular RNA in brain injury induced by inflammation in preterm mice: a preliminary study[J]. CJCP, 2021, 23(7): 730-734.
Yuan TM, Sun Y, Zhan CY, et al. Intrauterine infection/inflammation and perinatal brain damage:role of glial cells and toll-like receptor signaling[J]. J Neuroimmunol, 2010, 229(1-2):16-25. DOI:10.1016/j.jneuroim.2010.08.008. PMID:20826013.
[2]
Hagberg H, Mallard C, Ferriero DM, et al. The role of inflammation in perinatal brain injury[J]. Nat Rev Neurol, 2015, 11(4):192-208. DOI:10.1038/nrneurol.2015.13. PMID:25686754. PMCID:PMC4664161.
[3]
Salmaso N, Jablonska B, Scafidi J, et al. Neurobiology of premature brain injury[J]. Nat Neurosci, 2014, 17(3):341-346. DOI:10.1038/nn.3604. PMID:24569830. PMCID:PMC4106480.
[4]
Fancy SP, Harrington EP, Baranzini SE, et al. Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer[J]. Nat Neurosci, 2014, 17(4):506-512. DOI:10.1038/nn.3676. PMID:24609463. PMCID:PMC3975168.
[5]
Chen RJ, Piao XH, Xiao M, et al. Long noncoding RNAs interact with mRNAs:a new perspective on the mechanism of premature brain injury[J]. Neurosci Lett, 2019, 707:134274. DOI:10.1016/j.neulet.2019.05.028. PMID:31103728.
[6]
Wang F, Xiao M, Lin XJ, et al. Expression of heme oxygenase-1 and leukemia inhibitory factor in maternal plasma and placental tissue in a lipopolysaccharide-induced late pregnancy preterm birth mouse model[J]. J Reprod Med, 2016, 61(1-2):39-46. PMID:26995887.
[7]
Zhou CJ, Hou WH, Jiang DG, et al. Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders[J]. Neural Regen Res, 2020, 15(5):817-823. DOI:10.4103/1673-5374.268969. PMID:31719241. PMCID:PMC6990782..
[8]
Chen BJ, Huang S, Janitz M. Changes in circular RNA expression patterns during human foetal brain development[J]. Genomics, 2019, 111(4):753-758. DOI:10.1016/j.ygeno.2018.04.015. PMID:29709512.
[9]
Zhang TN, Yang N, Goodwin JE, et al. Characterization of circular RNA and microRNA profiles in septic myocardial depression:a lipopolysaccharide-induced rat septic shock model[J]. Inflammation, 2019, 42(6):1990-2002. DOI:10.1007/s10753-019-01060-8. PMID:31332662.
[10]
Xie F, Zhao Y, Wang SD, et al. Identification, characterization, and functional investigation of circular RNAs in subventricular zone of adult rat brain[J]. J Cell Biochem, 2019, 120(3):3428-3437. DOI:10.1002/jcb.27614. PMID:30246481.
[11]
Yang H, Wang H, Shang H, et al. Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer's disease[J]. Cell Cycle, 2019, 18(18):2197-2214. DOI:10.1080/15384101.2019.1629773. PMID:31373242. PMCID:PMC6738533.
[12]
Kleaveland B, Shi CY, Stefano J, et al. A network of noncoding regulatory RNAs acts in the mammalian brain[J]. Cell, 2018, 174(2):350-362.e17. DOI:10.1016/j.cell.2018.05.022. PMID:29887379. PMCID:PMC6559361.
[13]
Adorjan K, Falkai P. Premature mortality, causes of death, and mental disorders[J]. Lancet, 2019, 394(10211):1784-1786. DOI:10.1016/S0140-6736(19)32521-8. PMID:31668724.
Dou ZQ, Yu Q, Wang GY, et al. Circular RNA expression profiles alter significantly after intracerebral hemorrhage in rats[J]. Brain Res, 2020, 1726:146490. DOI:10.1016/j.brainres.2019.146490. PMID:31610150.
[16]
Bai Y, Zhang Y, Han B, et al. Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity[J]. J Neurosci, 2018, 38(1):32-50. DOI:10.1523/JNEUROSCI.1348-17.2017. PMID:29114076. PMCID:PMC6705810.
[17]
Bingol B, Sheng M. Deconstruction for reconstruction:the role of proteolysis in neural plasticity and disease[J]. Neuron, 2011, 69(1):22-32. DOI:10.1016/j.neuron.2010.11.006. PMID:21220096.
[18]
Qu Y, Zhu J, Liu JY, et al. Circular RNA circ_0079593 indicates a poor prognosis and facilitates cell growth and invasion by sponging miR-182 and miR-433 in glioma[J]. J Cell Biochem, 2019, 120(10):18005-18013. DOI:10.1002/jcb.29103. PMID:31148222.
[19]
Chen JX, Wang YP, Zhang X, et al. lncRNA Mtss1 promotes inflammatory responses and secondary brain injury after intracerebral hemorrhage by targeting miR-709 in mice[J]. Brain Res Bull, 2020, 162:20-29. DOI:10.1016/j.brainresbull.2020.04.017. PMID:32442560.
[20]
Li M, Chen H, Chen LX, et al. miR-709 modulates LPS-induced inflammatory response through targeting GSK-3β[J]. Int Immunopharmacol, 2016, 36:333-338. DOI:10.1016/j.intimp.2016.04.005. PMID:27232654.
[21]
Zhang WL, Chen L, Geng J, et al. β-elemene inhibits oxygen-induced retinal neovascularization via promoting miR-27a and reducing VEGF expression[J]. Mol Med Rep, 2019, 19(3):2307-2316. DOI:10.3892/mmr.2019.9863. PMID:30664207. PMCID:PMC6392088.
[22]
Jayson GC, Kerbel R, Ellis LM, et al. Antiangiogenic therapy in oncology:current status and future directions[J]. Lancet, 2016, 388(10043):518-529. DOI:10.1016/S0140-6736(15)01088-0. PMID:26853587.
