Welcome to International Network for Natural Sciences | INNSpub

In-silico analysis to identify role of 3′-UTR associated miRNAs in epilepsy syndromes

Research Paper | November 1, 2017

| Download 5

Epilepsy genes, miRNAs, RegRNA2, In-silico analysis, miRmap

Key Words:

Int. J. Biosci.11( 5), 337-345, November 2017

DOI: http://dx.doi.org/10.12692/ijb/11.5.337-345


IJB 2017 [Generate Certificate]


Epilepsy is a heterogeneous neurodevelopmental condition. Studying the expression profiles of regulatory molecules that may help to understand the pathogenesis of epilepsy and their regulatory control mechanism is important. MicroRNAs (miRNA) are small noncoding RNA molecules that control gene expression at post-transcriptional level. miRNA associated with untranslated regions (UTRs) of genes may alter the expression in the disease pathogenesis. The objective of present study was to predict the association of different miRNAs in the regulation of genes responsible for different types of epilepsies. In this study, we predicted some common miRNAs associated with 3′-UTR regions of about 30 selected epilepsies causative genes using RegRNA 2.0 an in-silico tool. The more common miRNA that have target sites within regulatory region in number of genes, were hsa-miR-644b-5p, hsa-miR-5193, hsa-miR-4449, hsa-miR-4646-3p, hsa-miR-4739, hsa-miR-766-3p, hsa-miR-2355-5p, hsa-miR-3943, hsa-miR-5006-3p, hsa-miR-574-5p, hsa-miR-4459, hsa-miR-298 and hsa-miR-4728-5p. Different validation scores were obtained from miRmap software, online. Further we analyzed the conservation of UTRs of the selected genes in the higher order mammals like, chimpanzee, gibbon, gorilla and macaca, and observed interesting results. The results of our study reinforce hypothesis that common miRNA may control the expression of different genes involved in epilepsies and regulate the function of respective protein. It may be proposed that miRNAs have role in the pathogenesis of epilepsy.


Copyright © 2017
By Authors and International Network for
Natural Sciences (INNSPUB)
This article is published under the terms of the Creative
Commons Attribution Liscense 4.0

In-silico analysis to identify role of 3′-UTR associated miRNAs in epilepsy syndromes

Alsharafi, WA, Xiao B, Abuhamed, MM, Luo Z. 2015. miRNAs: biological and clinical determinants in epilepsy. Frontiers in molecular neuroscience 8(59).

Aronica E, Fluiter K, Iyer A, Zurolo E, Vreijling J, Van Vliet E, Gorter J. 2010. Expression pattern of miR‐146a, an inflammation‐associated microrna, in experimental and human temporal lobe epilepsy. European journal of neuroscience 31(6), 1100-1107.

Barca-Mayo O, Tonelli DDP. 2014. Convergent microRNA actions coordinate neocortical development. Cellular and molecular life sciences 71(16), 2975-2995.

Berryer MH, Hamdan FF, Klitten LL, Møller RS, Carmant L, Schwartzentruber J, NeugnotCerioli M. 2013. Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. Human mutation 34(2), 385-394.

Boumil RM, Letts VA, Roberts MC, Lenz C, Mahaffey CL, Zhang ZW, Frankel WN. 2010. A missense mutation in a highly conserved alternate exon of dynamin-1 causes epilepsy in fitful mice. Plos genetics 6(8), e1001046.

Chen K, Rajewsky N. 2007. The evolution of gene regulation by transcription factors and micrornas. Nature reviews genetics 8(2), 93-103.

Dong L, Deng J, Sun ZM, Pan AP, Xiang XJ, Zhang L, Feng M. 2015. Interference with the β-catenin gene in gastric cancer induces changes to the miRNA expression profile. Tumor biology 36(9), 6973-6983.

Dorus S, Vallender EJ, Evans PD, Anderson JR, Gilbert SL, Mahowald M, Lahn BT. 2004. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119(7), 1027-1040.

Ebert MS, Sharp PA. 2012. Roles for microRNAs in conferring robustness to biological processes. Cell 149(3), 515-524.

Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Glynn M. 2014. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55(4), 475-482.

Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. 2011. miR-1254 and miR-574-5p: serum-based microrna biomarkers for early-stage non-small cell lung cancer. Journal of thoracic oncology 6(3), 482-488.

Griffiths-Jones S, Grocock RJ, Van Dongen S, Bateman A, Enright AJ. 2006. Mirbase: microRNA sequences, targets and gene nomenclature. Nucleic acids research 34(suppl 1), D140-D144.

Hu K, Xie YY, Zhang C, Ouyang DS, Long HY, Sun DN, Xiao B. 2012. Microrna expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus. BMC neuroscience 13(1), 1.

IUM T, 2012. ENCODE project writes eulogy for junk DNA.

Jimenez-Mateos E, Henshall D. 2013. Epilepsy and microRNA. Neuroscience 238, 218-229.

Kan AA, Van Erp S, Derijck AA, de Wit M, Hessel EV, O’Duibhir E, de Graan PN. 2012. Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response. Cellular and molecular life sciences 69(18), 3127-3145.

Krol J, Loedige I, Filipowicz W. 2010. The widespread regulation of microRNA biogenesis, function and decay. Nature reviews genetics 11(9), 597-610.

Maltseva DV, Galatenko VV, Samatov TR, Zhikrivetskaya SO, Khaustova NA, Nechaev IN, Kaprin AD. 2014. miRNome of inflammatory breast cancer. BMC research notes 7(1), 1.

Matta JA, Ashby MC, Sanz-Clemente A, Roche KW, Isaac JT. 2011. MGLUR5 and NMDA receptors drive the experience-and activity-dependent NMDA receptor NR2B to NR2A subunit switch. Neuron 70(2), 339-351.

Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Hornischer K. 2006. TRANSFAC® and its module transcompel®: transcriptional gene regulation in eukaryotes. Nucleic acids research 34(suppl 1), D108-D110.

Meng QL, Liu F, Yang XY, Liu XM, Zhang X, Zhang C, Zhang ZD. 2014. Identification of latent tuberculosis infection-related microRNAs in human U937 macrophages expressing Mycobacterium tuberculosis Hsp16. 3. BMC microbiology 14(1), 1.

Mignone F, Grillo G, Licciulli F, Iacono M, Liuni S, Kersey PJ, Pesole G. 2005. UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mrnaas. Nucleic acids research 33(suppl 1), D141-D146.

Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, Tohyama J. 2013. De Novo mutations in GNAO1, encoding a Gα o subunit of heterotrimeric G proteins, cause epileptic encephalopathy. The American journal of human genetics 93(3), 496-505.

Omran A, Peng J, Zhang C, Xiang QL, Xue J, Gan N, Yin F. 2012. Interleukin‐1β and microRNA‐146a in an immature rat model and children with mesial temporal lobe epilepsy. Epilepsia 53(7), 1215-1224.

Pal DK, Pong AW, Chung WK. 2010. Genetic evaluation and counseling for epilepsy. Nature reviews neurology 6(8), 445-453.

Palmieri F. 2004. The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflügers Archiv 447(5), 689-709.

Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, Bragin A. 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147(1), 235-246.

Pennisi E. 2012. ENCODE project writes eulogy for junk DNA. Science 337(6099), 1159-1161.

Roncon P, Soukupovà M, Binaschi A, Falcicchia C, Zucchini S, Ferracin M, Marucci G. 2015. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy–comparison with human epileptic samples. Scientific reports 5.

Scheffer AR, Holdenrieder S, Kristiansen G, von Ruecker A, Müller SC, Ellinger J. 2014. Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer? World journal of urology 32(2), 353-358.

Shimojima K, Sugawara M, Shichiji M, Mukaida S, Takayama R, Imai K, Yamamoto T. 2011. Loss-of-function mutation of collybistin is responsible for X-linked mental retardation associated with epilepsy. Journal of human genetics 56(8), 561-565.

Smirnova T, Stinnakre J, Mallet J. 1993. Characterization of a presynaptic glutamate receptor. Science 262(5132), 430-433.

Stamm S, Riethoven JJ, Le Texier V, Gopalakrishnan C, Kumanduri V, Tang Y, Thanaraj TA. 2006. ASD: a bioinformatics resource on alternative splicing. Nucleic acids research 34(suppl 1), D46-D55.

Swanberg SE, Nagarajan RP, Peddada S, Yasui DH, Lasalle JM. 2009. Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism. Human molecular genetics 18(3), 525-534.

Verstappen G, van Grunsven LA, Michiels C, Van de Putte T, Souopgui J, Van Damme J, Huylebroeck D. 2008. Atypical Mowat–Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NURD corepressor complex. Human molecular genetics 17(8), 1175-1183.

Xun M, Ma CF, Du QL, Ji YH, Xu JR. 2015.. Differential expression of miRNAs in enterovirus 71-infected cells. Virology journal 12(1), 1.