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Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis

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Abstract

The role of microglia in traumatic brain injury (TBI) has gained considerable attention. The present study aims to elucidate the potential mechanisms of Long intergenic non-protein coding RNA 707 (LINC00707) in TBI-induced microglia activation and inflammatory factor release. An in vivo model of rat TBI and in vitro microglia model was established using Controlled cortex injury (CCI) and lipopolysaccharide (LPS) stimulation. RT-qPCR to detect LINC00707 levels in rat cerebral cortex or cells. Modified Neurological Impairment Score (mNSS) and Morris Water Maze test was conducted to assess the neurological deficits and cognitive impairment. ELISA analysis of pro-inflammatory factors levels. CCK-8 and flow cytometry for cell viability and apoptosis levels. Dual-luciferase report and RIP assay to validate the targeting relationship between LINC00707 and miR-30a-5p. LINC00707 was elevated in the TBI rat cerebral cortex and LPS-induced microglia, while miR-30a-5p was noticeably decreased (P < 0.05). Increased mNSS, cognitive dysfunction, and brain edema in TBI rats were all prominently reversed by silencing of LINC00707, but this reversal was partially abrogated by decreasing miR-30a-5p (P < 0.05). Inhibition of LINC00707 suppressed the overproduction of inflammatory factors in TBI rats (P < 0.05). LPS decreased microglial cell viability, increased apoptosis, and promoted inflammatory overproduction than control, but the silencing of LINC00707 reversed its effect. Suppression of miR-30a-5p attenuated this reversal (P < 0.05). miR-30a-5p was the target miRNA of LINC00707. All in all, the results suggested that inhibiting LINC00707/miR-30a-5p axis could alleviate the progression of TBI by suppressing the inflammation and apoptosis of microglia cells.

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Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Herrero Babiloni A, Baril AA, Charlebois-Plante C, Jodoin M, Sanchez E, De Baets L, Arbour C, Lavigne GJ, Gosselin N, De Beaumont L (2023) The putative role of Neuroinflammation in the Interaction between traumatic brain injuries, Sleep, Pain and other neuropsychiatric outcomes: a state-of-the-art review. J Clin Med 12:1793. https://doi.org/10.3390/jcm12051793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Chen T, Xia Y, Zhang L, Xu T, Yi Y, Chen J, Liu Z, Yang L, Chen S, Zhou X, Chen X, Wu H, Liu J (2023) Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury. Mater Today Bio 19:100606. https://doi.org/10.1016/j.mtbio.2023.100606

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Yang ZL, Liang ZY, Lin YK, Lin FB, Rao J, Xu XJ, Wang CH, Chen CM (2023) Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: a systematic review and network meta-analysis. Front Neurosci 17:1147194. https://doi.org/10.3389/fnins.2023.1147194

    Article  PubMed  PubMed Central  Google Scholar 

  4. Grovola MR, von Reyn C, Loane DJ, Cullen DK (2023) Understanding microglial responses in large animal models of traumatic brain injury: an underutilized resource for preclinical and translational research. J Neuroinflammation 20:67. https://doi.org/10.1186/s12974-023-02730-z

    Article  PubMed  PubMed Central  Google Scholar 

  5. Meng J, Ding T, Chen Y, Long T, Xu Q, Lian W, Liu W (2021) LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p. Int Immunopharmacol 90:107141. https://doi.org/10.1016/j.intimp.2020.107141

    Article  PubMed  CAS  Google Scholar 

  6. Bourget C, Adams KV, Morshead CM (2022) Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke. J Neuroinflammation 19:146. https://doi.org/10.1186/s12974-022-02487-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Tripathi S, Shree B, Mohapatra S, Swati, Basu A, Sharma V (2021) The Expanding Regulatory Mechanisms and Cellular Functions of Long non-coding RNAs (lncRNAs) in Neuroinflammation. Mol Neurobiol 58:2916–2939. https://doi.org/10.1007/s12035-020-02268-8

    Article  PubMed  CAS  Google Scholar 

  8. Jin Y, Jiang L, Wang Y, Huang Y, Yu W, Ma X (2023) lncRNA PRR34-AS1 knockdown represses neuroinflammation and neuronal death in traumatic brain injury by inhibiting microRNA-498 expression. Brain Inj 1–10. https://doi.org/10.1080/02699052.2023.2192524

  9. Lei J, Zhang X, Tan R, Li Y, Zhao K, Niu H (2022) Levels of lncRNA GAS5 in plasma of patients with severe traumatic brain Injury: correlation with systemic inflammation and early outcome. J Clin Med 11:3319. https://doi.org/10.3390/jcm11123319

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Qian M, Shi Y, Lu W (2022) LINC00707 knockdown inhibits IL-1beta-induced apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes by the miR-330-5p/FSHR axis. Immunopharmacol Immunotoxicol 44:671–681. https://doi.org/10.1080/08923973.2022.2076241

    Article  PubMed  CAS  Google Scholar 

  11. Chen L, Chen Y, Huang J, Zhang J (2022) LncRNA LINC00707 serves as a sponge of mir-382-5p to alleviate lipopolysaccharide (LPS)-induced WI-38 cell injury through upregulating NKAP in infantile pneumonia. Autoimmunity 55:328–338. https://doi.org/10.1080/08916934.2022.2062594

    Article  PubMed  CAS  Google Scholar 

  12. Zhu S, Zhou Z, Li Z, Shao J, Jiao G, Huang YE, Lin Y (2019) Suppression of LINC00707 alleviates lipopolysaccharide-induced inflammation and apoptosis in PC-12 cells by regulated miR-30a-5p/Neurod 1. Biosci Biotechnol Biochem 83:2049–2056. https://doi.org/10.1080/09168451.2019.1637245

    Article  PubMed  CAS  Google Scholar 

  13. Hwang I, Ha SW, Han JH (2017) Unusual FDG-PET findings in traumatic Brain Injury; did traumatic Brain Injury Provoke Rapid Progression of Alzheimer’s Disease? Dement Neurocogn Disord 16:54–55. https://doi.org/10.12779/dnd.2017.16.2.54

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sun T, Zhao K, Liu M, Cai Z, Zeng L, Zhang J, Li Z, Liu R (2022) miR-30a-5p induces abeta production via inhibiting the nonamyloidogenic pathway in Alzheimer’s disease. Pharmacol Res 178:106153. https://doi.org/10.1016/j.phrs.2022.106153

    Article  PubMed  CAS  Google Scholar 

  15. Zhou X, Wang Z, Xu B, Ji N, Meng P, Gu L, Li Y (2021) Long non-coding RNA NORAD protects against cerebral ischemia/reperfusion injury induced brain damage, cell apoptosis, oxidative stress and inflammation by regulating miR-30a-5p/YWHAG. Bioengineered 12:9174–9188. https://doi.org/10.1080/21655979.2021.1995115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Wang P, Zhang N, Liang J, Li J, Han S, Li J (2015) Micro-RNA-30a regulates ischemia-induced cell death by targeting heat shock protein HSPA5 in primary cultured cortical neurons and mouse brain after stroke. J Neurosci Res 93:1756–1768. https://doi.org/10.1002/jnr.23637

    Article  PubMed  CAS  Google Scholar 

  17. Li XL, Wang B, Yang FB, Chen LG, You J (2022) HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury. Neural Regen Res 17:1096–1105. https://doi.org/10.4103/1673-5374.322645

    Article  PubMed  CAS  Google Scholar 

  18. Li J, Gao W, Zhao Z, Li Y, Yang L, Wei W, Ren F, Li Y, Yu Y, Duan W, Li J, Dai B, Guo R (2022) Ginsenoside Rg1 reduced Microglial activation and mitochondrial dysfunction to Alleviate Depression-Like Behaviour Via the GAS5/EZH2/SOCS3/NRF2 Axis. Mol Neurobiol 59:2855–2873. https://doi.org/10.1007/s12035-022-02740-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Zheng Z, Wang S, Wu C, Cao Y, Gu Q, Zhu Y, Zhang W, Hu W (2022) Gut microbiota dysbiosis after traumatic brain Injury contributes to Persistent Microglial Activation Associated with upregulated Lyz2 and shifted Tryptophan Metabolic phenotype. https://doi.org/10.3390/nu14173467. Nutrients 14

  20. Xuan C, Cui H, Jin Z, Yue Y, Cao S, Cui S, Xu D (2023) Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats. Front Pharmacol 14:1096309. https://doi.org/10.3389/fphar.2023.1096309

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Feng L, Luo G, Li Y, Zhang C, Liu Y, Liu Y, Chen H, He D, Zhu Y, Gan L (2023) Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis. Vet Res 54:25. https://doi.org/10.1186/s13567-023-01149-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Lin YW, Fang CH, Meng FQ, Ke CJ, Lin FH (2020) Hyaluronic Acid loaded with Cerium Oxide Nanoparticles as antioxidant in Hydrogen Peroxide Induced Chondrocytes Injury: an in Vitro Osteoarthritis Model. Molecules 25. https://doi.org/10.3390/molecules25194407

  23. Zhang F, Yang Y, Chen X, Liu Y, Hu Q, Huang B, Liu Y, Pan Y, Zhang Y, Liu D, Liang R, Li G, Wei Q, Li L, Jin L (2021) The long non-coding RNA betaFaar regulates islet beta-cell function and survival during obesity in mice. Nat Commun 12:3997. https://doi.org/10.1038/s41467-021-24302-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Zhang L, Dong MN, Deng J, Zhang CH, Liu MW (2022) Resveratrol exhibits neuroprotection against paraquat-induced PC12 cells via heme oxygenase 1 upregulation by decreasing MiR-136-5p expression. Bioengineered 13:7065–7081. https://doi.org/10.1080/21655979.2022.2045764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Wu X, Wei H, Wu JQ (2022) Coding and long non-coding gene expression changes in the CNS traumatic injuries. Cell Mol Life Sci 79:123. https://doi.org/10.1007/s00018-021-04092-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Liu N, Sun H, Li X, Cao W, Peng A, Dong S, Yu Z (2021) Downregulation of lncRNA KCNQ1OT1 relieves traumatic brain injury induced neurological deficits via promoting M2 microglia polarization. Brain Res Bull 171:91–102. https://doi.org/10.1016/j.brainresbull.2021.03.004

    Article  PubMed  CAS  Google Scholar 

  27. Yi M, Dai X, Li Q, Xu X, Chen Y, Wang D (2019) Downregulated lncRNA CRNDE contributes to the enhancement of nerve repair after traumatic brain injury in rats. Cell Cycle 18:2332–2343. https://doi.org/10.1080/15384101.2019.1647024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Zou X, Gao C, Shang R, Chen H, Wang B (2021) Knockdown of lncRNA LINC00707 alleviates LPS-induced injury in MRC-5 cells by acting as a ceRNA of miR-223-5p. Biosci Biotechnol Biochem 85:315–323. https://doi.org/10.1093/bbb/zbaa069

    Article  PubMed  Google Scholar 

  29. Zhao W, Huang G, Ye J (2023) LINC00707 inhibits myocardial fibrosis and immune disorder in rheumatic heart disease by regulating miR-145-5p/S1PR1. Biotechnol Genet Eng Rev 1–14. https://doi.org/10.1080/02648725.2023.2204598

  30. Yang S, Xu J, Zeng X (2018) A six-long non-coding RNA signature predicts prognosis in melanoma patients. Int J Oncol 52:1178–1188. https://doi.org/10.3892/ijo.2018.4268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Yu S, Ruan X, Liu X, Zhang F, Wang D, Liu Y, Yang C, Shao L, Liu Q, Zhu L, Lin Y, Xue Y (2021) HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis. Cell Death Dis 12:153. https://doi.org/10.1038/s41419-021-03432-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Li H, Xu G, Yuan G (2022) Effects of an Armillaria mellea Polysaccharide on Learning and Memory of D-Galactose-Induced Aging mice. Front Pharmacol 13:919920. https://doi.org/10.3389/fphar.2022.919920

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Sozda CN, Larson MJ, Kaufman DA, Schmalfuss IM, Perlstein WM (2011) Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study. Int J Psychophysiol 82:97–106. https://doi.org/10.1016/j.ijpsycho.2011.06.019

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cederberg D, Harrington BM, Vlok AJ, Siesjo P (2022) Effect of antisecretory factor, given as a food supplement to adult patients with severe traumatic brain injury (SASAT): protocol for an exploratory randomized double blind placebo-controlled trial. Trials 23:340. https://doi.org/10.1186/s13063-022-06275-z

    Article  PubMed  PubMed Central  Google Scholar 

  35. Jiang H, Yang X, Wang Y, Zhou C (2022) Vitamin D protects against traumatic brain Injury via modulating TLR4/MyD88/NF-kappaB pathway-mediated microglial polarization and neuroinflammation. Biomed Res Int 2022:3363036. https://doi.org/10.1155/2022/3363036

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Liu N, Li Y, Jiang Y, Shi S, Niamnud A, Vodovoz SJ, Katakam PVG, Vidoudez C, Dumont AS, Wang X (2023) Establishment and application of a Novel in Vitro Model of Microglial Activation in Traumatic Brain Injury. J Neurosci 43:319–332. https://doi.org/10.1523/JNEUROSCI.1539-22.2022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Tang W, Chai W, Du D, Xia Y, Wu Y, Jiang L, Cheng C, Guo Z, Sun X, Huang Z, Zhong J (2022) The lncRNA-AK046375 Upregulates Metallothionein-2 by sequestering mir-491-5p to relieve the Brain oxidative stress Burden after Traumatic Brain Injury. Oxid Med Cell Longev 2022:8188404. https://doi.org/10.1155/2022/8188404

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Han K, Kang N, Yu X, Lu J, Ma Y (2022) lncRNA NEAT1-let 7b-P21 axis mediates the proliferation of neural stem cells cultured in vitro promoted by radial extracorporeal shock wave. Regen Ther 21:139–147. https://doi.org/10.1016/j.reth.2022.06.006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Wang P, Liang J, Li Y, Li J, Yang X, Zhang X, Han S, Li S, Li J (2014) Down-regulation of miRNA-30a alleviates cerebral ischemic injury through enhancing beclin 1-mediated autophagy. Neurochem Res 39:1279–1291. https://doi.org/10.1007/s11064-014-1310-6

    Article  PubMed  CAS  Google Scholar 

  40. Zhang Y, Cai S, Ding X, Lu C, Wu R, Wu H, Shang Y, Pang M (2021) MicroRNA-30a-5p silencing polarizes macrophages toward M2 phenotype to alleviate cardiac injury following viral myocarditis by targeting SOCS1. Am J Physiol Heart Circ Physiol 320:H1348–H1360. https://doi.org/10.1152/ajpheart.00431.2020

    Article  PubMed  CAS  Google Scholar 

  41. Yang F, Li WB, Qu YW, Gao JX, Tang YS, Wang DJ, Pan YJ (2020) Bone marrow mesenchymal stem cells induce M2 microglia polarization through PDGF-AA/MANF signaling. World J Stem Cells 12:633–658. https://doi.org/10.4252/wjsc.v12.i7.633

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gusar VA, Timofeeva AV, Zhanin IS, Shram SI, Pinelis VG (2017) [Estimation of time-dependent microRNA expression patterns in Brain tissue, Leukocytes, and blood plasma of rats under Photochemically Induced Focal Cerebral Ischemia]. Mol Biol (Mosk) 51:683–695. https://doi.org/10.7868/S0026898417040103

    Article  PubMed  CAS  Google Scholar 

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  1. Wei Hu and Jiang Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Taizhou Hospital of Wenzhou Medical University, No.1, Tongyang East Road, Taizhou, 317000, China

    Wei Hu, Yiqing Jiang & Xiaoming Hu

  2. Department of Neurosurgery, Taizhou Enze Medical Center, Enze Hospital, Taizhou, 318050, China

    Jiang Zhou & Zeyu Bao

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Contributions

W. H and J. Z designed the research study. Y.Q. J, Z.Y. B and X.M. H performed the research. W. H and J. Z analyzed the data. W. H and J. Z wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

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Correspondence to Wei Hu.

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This experiment was conducted with approval of the Animal Ethics Committee of Taizhou Hospital of Wenzhou Medical University. All institutional and national guidelines for the care and use of laboratory animals were followd. Appropriate measures were taken to minimize the number and suffering of animals.

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11064_2023_4029_MOESM1_ESM.tif

Additional File 1: Supplemental Figures. Effects of LINC00707 on BV2 cell activity, apoptosis, and inflammation. A. RT-qPCR analysis of the expression of LINC00707 after transfection with LINC00707 knockdown lentivirus in BV2. Detection of viability, apoptosis, and proinflammatory factor secretion in BV2 cells under low-expression of LINC00707 using CCK-8 (B), flow cytometry (C), and ELISA assay (D). *P < 0.05, **P < 0.01, ***P < 0.001 vs. LV-shNC.

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Hu, W., Zhou, J., Jiang, Y. et al. Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis. Neurochem Res 49, 222–233 (2024). https://doi.org/10.1007/s11064-023-04029-0

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