Abstract
The aim of this study was to analyze the expression profiles of the microRNAs (miRNAs) miR-145, miR-181c, miR-199a and miR-1183 in the hippocampus and blood of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate whether these can be used as diagnosis and prognosis biomarkers for epilepsy. Hippocampus and blood samples were collected from 20 patients with MTLE-HS, ten of whom had a favorable surgical outcome (Engel I) and ten with an unfavorable surgical outcome (Engel III-IV). Hippocampus samples from autopsied individuals with no neurological or psychiatric medical history (necropsy samples) and blood samples from healthy individuals were used as controls. Real-time quantitative PCR (RQ-PCR) was used to analyze miRNA expression. The results showed that the expressions of these miRNAs differed quantitatively in the hippocampus and blood of patients with MTLE-HS in comparison to the respective control. This difference was most pronounced for miR-145, which was hypo-expressed in the hippocampus and hyper-expressed in the blood of MTLE-HS patients. MiRNAs miR-145, miR-181c, miR-199a and miR-1183 were hyper-expressed in the blood of patients with MTLE-HS. No statistical differences in the levels of these miRNAs in the blood or hippocampus were found between Engel I patients and Engel III-IV patients. These results suggest that the analyzed microRNAs are potential circulating biomarkers for epilepsy diagnosis.
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References
Armand-Labit V, Pradines A (2017) Circulating cell-free microRNAs as clinical cancer biomarkers. Biomol Concepts 8:61–81. https://doi.org/10.1515/bmc-2017-0002
Avansini SH, de Sousa Lima BP, Secolin R et al (2017) MicroRNA hsa-miR-134 is a circulating biomarker for mesial temporal lobe epilepsy. PLoS One 12:e0173060. https://doi.org/10.1371/journal.pone.0173060
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bien CG, Kurthen M, Baron K et al (2001) Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study. Epilepsia 42:1416–1421
Blümcke I, Coras R, Miyata H, Ozkara C (2012) Defining clinico-neuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis. Brain Pathol 22:402–411. https://doi.org/10.1111/j.1750-3639.2012.00583.x
Brennan GP, Henshall DC (2018) microRNAs in the pathophysiology of epilepsy. Neurosci Lett 667:47–52. https://doi.org/10.1016/j.neulet.2017.01.017
Busillo JM, Benovic JL (2007) Regulation of CXCR4 signaling. Biochim Biophys Acta 1768:952–963. https://doi.org/10.1016/j.bbamem.2006.11.002
Cattani AA, Allene C, Seifert V et al (2016) Involvement of microRNAs in epileptogenesis. Epilepsia 57:1015–1026. https://doi.org/10.1111/epi.13404
Cendes F, Sakamoto AC, Spreafico R et al (2014) Epilepsies associated with hippocampal sclerosis. Acta Neuropathol 128:21–37. https://doi.org/10.1007/s00401-014-1292-0
Cerri C, Genovesi S, Allegra M et al (2016) The chemokine CCL2 mediates the seizure-enhancing effects of systemic inflammation. J Neurosci 36:3777–3788. https://doi.org/10.1523/JNEUROSCI.0451-15.2016
Chen C-L, Liu H, Guan X (2013) Changes in microRNA expression profile in hippocampus during the acquisition and extinction of cocaine-induced conditioned place preference in rats. J Biomed Sci 20:96. https://doi.org/10.1186/1423-0127-20-96
Della Vittoria Scarpati G, Falcetta F, Carlomagno C et al (2012) A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 83:1113–1119. https://doi.org/10.1016/j.ijrobp.2011.09.030
Dey A, Kang X, Qiu J et al (2016) Anti-inflammatory small molecules to treat seizures and epilepsy: from bench to bedside. Trends Pharmacol Sci 37:463–484. https://doi.org/10.1016/j.tips.2016.03.001
Dogini DB, Avansini SH, Vieira AS, Lopes-Cendes I (2013) MicroRNA regulation and dysregulation in epilepsy. Front Cell Neurosci 7:172. https://doi.org/10.3389/fncel.2013.00172
Engel JJ, Van Ness PC, Rasmussen TB, Ojemann LM (1993) Outcome with respect to epileptic seizures. In: Engel JJ (ed) Surgical treatment of the epilepsies, 2nd edn. Raven Press, New York, pp 609–621
Fiest KM, Sauro KM, Wiebe S et al (2017) Prevalence and incidence of epilepsy. Neurology 88:296–303. https://doi.org/10.1212/WNL.0000000000003509
Galimberti D, Villa C, Fenoglio C et al (2014) Circulating miRNAs as potential biomarkers in Alzheimer’s disease. J Alzheimers Dis 42:1261–1267. https://doi.org/10.3233/JAD-140756
Gan CS, Wang CW, Tan KS (2012) Circulatory microRNA-145 expression is increased in cerebral ischemia. Genet Mol Res 11:147–152. https://doi.org/10.4238/2012.January.27.1
Hu Y, Ehli EA, Boomsma DI (2017) MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum disorder: current progress in genetic association studies, expression profiling, and translational research. Autism Res 10(7):1184–1203. https://doi.org/10.1002/aur.1789
Hua Y-J, Tang Z-Y, Tu K et al (2009) Identification and target prediction of miRNAs specifically expressed in rat neural tissue. BMC Genomics 10:214. https://doi.org/10.1186/1471-2164-10-214
Jiang L, Zhang C, Li Y et al (2011) A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population. Breast Cancer Res Treat 126:487–495. https://doi.org/10.1007/s10549-010-1094-6
Jiang Y, Zhang M, He H et al (2013) MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm. BMC Med Genet 6:36. https://doi.org/10.1186/1755-8794-6-36
Jiang G, Zhou R, He X et al (2016) Expression levels of microRNA-199 and hypoxia-inducible factor-1 alpha in brain tissue of patients with intractable epilepsy. Int J Neurosci 126:326–334. https://doi.org/10.3109/00207454.2014.994209
Keller A, Leidinger P, Lange J et al (2009) Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One 4:e7440. https://doi.org/10.1371/journal.pone.0007440
Li M-M, Li X-M, Zheng X-P et al (2014) MicroRNAs dysregulation in epilepsy. Brain Res 1584:94–104. https://doi.org/10.1016/j.brainres.2013.09.049
Li N, Lian J, Zhao S et al (2015) Detection of differentially expressed MicroRNAs in rheumatic heart disease: miR-1183 and miR-1299 as potential diagnostic biomarkers. Biomed Res Int 2015:1–11. https://doi.org/10.1155/2015/524519
Liu D-Z, Tian Y, Ander BP et al (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101. https://doi.org/10.1038/jcbfm.2009.186
Marchi N, Granata T, Janigro D (2014) Inflammatory pathways of seizure disorders. Trends Neurosci 37:55–65. https://doi.org/10.1016/j.tins.2013.11.002
Margis R, Margis R, Rieder CRM (2011) Identification of blood microRNAs associated to Parkinson’s disease. J Biotechnol 152:96–101. https://doi.org/10.1016/j.jbiotec.2011.01.023
Risbud RM, Porter BE (2013) Changes in microRNA expression in the whole hippocampus and hippocampal synaptoneurosome fraction following pilocarpine induced status epilepticus. PLoS One 8:e53464. https://doi.org/10.1371/journal.pone.0053464
Shen C-H, Zhang Y-X, Zheng Y et al (2019) Expression of plasma microRNA-145-5p and its correlation with clinical features in patients with refractory epilepsy. Epilepsy Res 154:21–25. https://doi.org/10.1016/j.eplepsyres.2019.04.010
Siomi H, Siomi MC (2010) Posttranscriptional regulation of MicroRNA biogenesis in animals. Mol Cell 38:323–332. https://doi.org/10.1016/j.molcel.2010.03.013
Sun J, Cheng W, Liu L et al (2016) Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure. Mol Med Rep 14:5318–5324. https://doi.org/10.3892/mmr.2016.5906
Surges R, Kretschmann A, Abnaof K et al (2016) Changes in serum miRNAs following generalized convulsive seizures in human mesial temporal lobe epilepsy. Biochem Biophys Res Commun 481:13–18. https://doi.org/10.1016/j.bbrc.2016.11.029
Tominaga N, Kosaka N, Ono M et al (2015) Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun 6:6716. https://doi.org/10.1038/ncomms7716
Tumilson CA, Lea RW, Alder JE, Shaw L (2014) Circulating microRNA biomarkers for glioma and predicting response to therapy. Mol Neurobiol 50:545–558. https://doi.org/10.1007/s12035-014-8679-8
Vezzani A, Friedman A, Dingledine RJ (2013) The role of inflammation in epileptogenesis. Neuropharmacology 69:16–24. https://doi.org/10.1016/j.neuropharm.2012.04.004
Wang J, Tan L, Tan L et al (2015a) Circulating microRNAs are promising novel biomarkers for drug-resistant epilepsy. Sci Rep 5:10201. https://doi.org/10.1038/srep10201
Wang J, Yu J-T, Tan L et al (2015b) Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy. Sci Rep 5:9522. https://doi.org/10.1038/srep09522
Weiland M, Gao X-H, Zhou L, Mi Q-S (2012) Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol 9:850–859. https://doi.org/10.4161/rna.20378
Wieser H-G, ILAE Commission on Neurosurgery of Epilepsy (2004) ILAE commission report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 45:695–714. https://doi.org/10.1111/j.0013-9580.2004.09004.x
Wieser HG, Ortega M, Friedman A, Yonekawa Y (2003) Long-term seizure outcomes following amygdalohippocampectomy. J Neurosurg 98:751–763. https://doi.org/10.3171/jns.2003.98.4.0751
Wu X-J, Pu X-M, Zhao Z-F et al (2015) The expression profiles of microRNAs in Kaposi’s sarcoma. Tumour Biol 36:437–446. https://doi.org/10.1007/s13277-014-2626-1
Yan S, Zhang H, Xie W et al (2017) Altered microRNA profiles in plasma exosomes from mesial temporal lobe epilepsy with hippocampal sclerosis. Oncotarget 8:4136–4146. https://doi.org/10.18632/oncotarget.13744
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Luana Grupioni Lourenço Antônio assisted in writing of the manuscript and was responsible for data acquisition and interpretation. Priscila Freitas-Lima, João Alberto Assirati Jr, Caio Marconato Matias, Mucio Luiz de Assis Cirino, Luis Fernando Tirapelli and Gabriela Pereira-da-Silva assisted in writing the manuscript. Tonicarlo Rodrigues Velasco, Americo Ceiki Sakamoto and Carlos Gilberto Carlotti Jr contributed substantially to the scientific and intellectual contents of the study. Daniela Pretti da Cunha Tirapelli was responsible for concept design and intellectual and scientific content of the study, supervised all phases of the study and critically reviewed the study and manuscript.
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Antônio, L.G.L., Freitas-Lima, P., Pereira-da-Silva, G. et al. Expression of MicroRNAs miR-145, miR-181c, miR-199a and miR-1183 in the Blood and Hippocampus of Patients with Mesial Temporal Lobe Epilepsy. J Mol Neurosci 69, 580–587 (2019). https://doi.org/10.1007/s12031-019-01386-w
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DOI: https://doi.org/10.1007/s12031-019-01386-w