Sıçanlarda Deneysel Omurilik Yaralanmasında miR-30a ve miR-17 Biyomarkerları ve Metilprednizolonun Etkileri
Araştırma Makalesi
DOI:
https://doi.org/10.5281/zenodo.8325077Anahtar Kelimeler:
miRNA, metilprednizolon, omurilik yaralanması, miR-30a, miR-17Özet
Giriş: Metilprednizolon, omurilik yaralanması sonrası erken dönemde inflamasyon, hücre kan akımı değişiklikleri ve apoptoz gibi birçok etkili mekanizmaya sahip nöroprotektif bir steroiddir. Bu çalışma, genomik regülasyonda rol oynadığı tahmin edilen mikroRNA ifadeleri aracılığıyla metilprednizolonun erken hasarı önlemedeki inhibitör aktivitesini göstermeyi amaçlamıştır.
Yöntem: Bu çalışma 56 adet erkek Sprague-Dawley cinsi sıçan üzerinde yapılmıştır. Tüm hayvanlar, her biri 7 hayvandan oluşan 8 gruba ayrıldı. T5-8 seviyeleri arasında laminektomi işlemi uygulandı. İki kontrol grubu dışındaki tüm gruplara T5 seviyesinden 1 dakika süreyle Yaşargil anevrizma klipsi ile hasar verildi. Klipslemeden 6, 12 ve 24. saatlerde T5-8 omurilik dokusu alındı. Sadece kliplenen gruplara intraperitoneal kaviteye metilprednizolon verildi. Histopatolojik ve immünohistokimyasal inceleme sonucunda metilprednizolon verilen gruplarda hücre nekrozu, ödem, kanama ve beyaz cevher-gri madde geçişinde anlamlı azalma oldu. Tüm sıçanlardan eksize edilen hasarlı omurilik örnekleri. miR-30a ve miR-17 gen ekspresyon seviyeleri kantitatif PCR yöntemi ile değerlendirildi.
Bulgular: miR-30a, omurilik yaralanmasından sonra 12. ve 24. saatlerde önemli ölçüde yukarı regüle edildi ve bu artış metilprednizolon ile tedavi edilen gruplarda sınırlıydı. miR-17, 6. saatte aşağı regüle edildi ve 12. saatte en düşük seviyesine ulaştı.
Sonuç: Metilprednisolon, miR-30a ve miR-17 mekanizması aracılığıyla omurilik yaralanmasında istatistiksel olarak anlamlı iyileştirici etkilere sahiptir.
Referanslar
Kang Y, Ding H, Zhou H, et al. Epidemiology of worldwide spinal cord injury: a literature review. Journal of Neurorestoratology. 2017;Volume 6:1-9. doi:10.2147/jn.s143236
Hamilton MG, Mylks ST. Pediatric spinal injury: review of 174 hospital admissions. Journal of Neurosurgery. 1992;77(5):700-704. doi:10.3171/jns.1992.77.5.0700
Guttmann L. Spinal Cord Injuries. Comprehensive Management and Research. London, England: Blackwell Scientific Publications; 1976: 4–7.
Ning GZ, Wu Q, Li YL, Feng SQ. Epidemiology of traumatic spinal cord injury in Asia: a systematic review. J Spinal Cord Med. 2012;35(4):229–239.
Nardone R, Florea C, Höller Y, et al. Rodent, large animal and non-human primate models of spinal cord injury. Zoology (Jena). 2017;123:101-114. doi:10.1016/j.zool.2017.06.004
Kwon BK, Oxland TR, Tetzlaff W. Animal models used in spinal cord regeneration research. Spine (Phila Pa 1976). 2002;27(14):1504-1510.doi:10.1097/00007632-200207150-00005
Noble LJ, Wrathall JR. Spinal cord contusion in the rat: morphometric analyses of alterations in the spinal cord. Exp Neurol. 1985;88(1):135-149. doi:10.1016/0014-4886(85)90119-0
Metz GA, Curt A, van de Meent H, Klusman I, Schwab ME, Dietz V. Validation of the weight-drop contusion model in rats: a comparative study of human spinal cord injury. J Neurotrauma. 2000;17(1):1-17. doi:10.1089/neu.2000.17.1
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297. doi:10.1016/s0092-8674(04)00045-5
Lai EC, Tomancak P, Williams RW, Rubin GM. Computational identification of Drosophila microRNA genes. Genome Biol. 2003;4(7):R42. doi:10.1186/gb-2003-4-7-r42
Lim LP, Lau NC, Weinstein EG, et al. The microRNAs of Caenorhabditis elegans. Genes Dev. 2003;17(8):991-1008. doi:10.1101/gad.1074403
Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP. Vertebrate microRNA genes. Science. 2003;299(5612):1540. doi:10.1126/science.1080372
Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005;11(3):241-247. doi:10.1261/rna.7240905
Fu G, Brkic J, Hayder H, Peng C. MicroRNAs in human placental development and pregnancy complications. Int J Mol Sci. (2013) 14:5519–44.
Tüfekci KU, Oner MG, Meuwissen RL, Genç S. The role of microRNAs in human diseases. Methods Mol Biol. 2014;1107:33-50. doi:10.1007/978-1-62703-748-8_3
Paul P, Chakraborty A, Sarkar D, et al. Interplay between miRNAs and human diseases. J Cell Physiol. 2018;233(3):2007-2018. doi:10.1002/jcp.25854
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20(8):460-469. doi:10.1016/j.molmed.2014.06.005
Wang J, Chen J, Sen S. MicroRNA as Biomarkers and Diagnostics. J Cell Physiol. 2016;231(1):25-30. doi:10.1002/jcp.25056
Huang W. MicroRNAs: Biomarkers, Diagnostics, and Therapeutics. Methods Mol Biol. 2017;1617:57-67. doi:10.1007/978-1-4939-7046-9_4
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol.2014;15:509–24.
de Rie D, Abugessaisa I, Alam T, et al. An integrated expression atlas of miRNAs and their promoters in human and mouse. Nat Biotechnol. 2017;35(9):872-878. doi:10.1038/nbt.3947
Kim YK, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26(3):775-783. doi:10.1038/sj.emboj.7601512
Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol. 2004;339(2):327-335. doi:10.1016/j.jmb.2004.03.065
O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402. Published 2018 Aug 3. doi:10.3389/fendo.2018.00402
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011;12(2):99-110. doi:10.1038/nrg2936
Ipsaro JJ, Joshua-Tor L. From guide to target: molecular insights into eukaryotic RNA-interference machinery. Nat Struct Mol Biol. 2015;22(1):20-28. doi:10.1038/nsmb.2931
Xu W, San Lucas A, Wang Z, Liu Y. Identifying microRNA targets in different gene regions. BMC Bioinformatics. 2014;15 Suppl 7(Suppl 7):S4. doi:10.1186/1471-2105-15-S7-S4
Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008;105(39):14879-14884. doi:10.1073/pnas.0803230105
Zhang J, Zhou W, Liu Y, Liu T, Li C, Wang L. Oncogenic role of microRNA-532-5p in human colorectal cancer via targeting of the 5'UTR of RUNX3. Oncol Lett. 2018;15(5):7215-7220. doi:10.3892/ol.2018.8217
Kato M, Slack FJ. microRNAs: small molecules with big roles - C. elegans to human cancer. Biol Cell. 2008;100(2):71-81. doi:10.1042/BC20070078
Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25-36. doi:10.1016/s0092-8674(03)00231-9
Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell. 2000;5(4):659-669. doi:10.1016/s1097-2765(00)80245-2
Abrahante JE, Daul AL, Li M, et al. The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell. 2003;4(5):625-637. doi:10.1016/s1534-5807(03)00127-8
Moss EG, Lee RC, Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997;88(5):637-646. doi:10.1016/s0092-8674(00)81906-6
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843-854. doi:10.1016/0092-8674(93)90529-y
Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 2003;426(6968):845-849. doi:10.1038/nature02255
Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature2005; 436: 214-220.
Stark A, Brennecke J, Russell RB, Cohen SM. Identification of Drosophila MicroRNA targets. PLoS Biol. 2003;1(3):E60. doi:10.1371/journal.pbio.0000060
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524-15529. doi:10.1073/pnas.242606799
Poy MN, Eliasson L, Krutzfeldt J, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432(7014):226-230. doi:10.1038/nature03076
Giraldez AJ, Cinalli RM, Glasner ME, et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science. 2005;308(5723):833-838. doi:10.1126/science.1109020
Young W, Flamm ES. Effect of high-dose corticosteroid therapy on blood flow, evoked potentials, and extracellular calcium in experimental spinal injury. J Neurosurg. 1982;57(5):667-673. doi:10.3171/jns.1982.57.5.0667
Anderson DK, Saunders RD, Demediuk P, et al. Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium. Cent Nerv Syst Trauma. 1985;2(4):257-267. doi:10.1089/cns.1985.2.257
Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA. 1997;277(20):1597-1604.
Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010;220(2):126-139. doi:10.1002/path.2638
Kosik KS. The neuronal microRNA system. Nat Rev Neurosci. 2006;7(12):911-920. doi:10.1038/nrn2037
Bilen J, Liu N, Burnett BG, Pittman RN, Bonini NM. MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol Cell. 2006;24(1):157-163. doi:10.1016/j.molcel.2006.07.030
Bak M, Silahtaroglu A, Møller M, et al. MicroRNA expression in the adult mouse central nervous system. RNA. 2008;14(3):432-444. doi:10.1261/rna.783108
Liu NK, Wang XF, Lu QB, Xu XM. Altered microRNA expression following traumatic spinal cord injury. Exp Neurol. 2009;219(2):424-429. doi:10.1016/j.expneurol.2009.06.015
Liu J. Control of protein synthesis and mRNA degradation by microRNAs. Curr Opin Cell Biol. 2008;20(2):214-221. doi:10.1016/j.ceb.2008.01.006
Nakanishi K, Nakasa T, Tanaka N, et al. Responses of microRNAs 124a and 223 following spinal cord injury in mice. Spinal Cord. 2010;48(3):192-196. doi:10.1038/sc.2009.89
Yunta M, Nieto-Díaz M, Esteban FJ, et al. MicroRNA dysregulation in the spinal cord following traumatic injury. PLoS One. 2012;7(4):e34534. doi:10.1371/journal.pone.0034534
Jee MK, Jung JS, Choi JI, et al. MicroRNA 486 is a potentially novel target for the treatment of spinal cord injury [published correction appears in Brain. 2013 Aug;136(Pt 8):2643]. Brain. 2012;135(Pt 4):1237-1252. doi:10.1093/brain/aws047
Budde H, Schmitt S, Fitzner D, Opitz L, Salinas-Riester G, Simons M. Control of oligodendroglial cell number by the miR-17-92 cluster. Development. 2010;137(13):2127-2132. doi:10.1242/dev.050633
Chang TC, Yu D, Lee YS, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008;40(1):43-50. doi:10.1038/ng.2007.30
Hong P, Jiang M, Li H. Functional requirement of dicer1 and miR-17-5p in reactive astrocyte proliferation after spinal cord injury in the mouse. Glia. 2014;62(12):2044-2060. doi:10.1002/glia.22725
Wei W, Yang Y, Cai J, et al. MiR-30a-5p Suppresses Tumor Metastasis of Human Colorectal Cancer by Targeting ITGB3. Cell Physiol Biochem. 2016;39(3):1165-1176. doi:10.1159/000447823
Saravanan S, Thirugnanasambantham K, Hanieh H, et al. miRNA-24 and miRNA-466i-5p controls inflammation in rat hepatocytes. Cell Mol Immunol. 2015;12(1):113-115. doi:10.1038/cmi.2014.67
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