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Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

Integrated In-silico Analysis to Study the Role of microRNAs in the Detection of Chronic Kidney Diseases

Author(s): Amina Khan, Andleeb Zahra, Sana Mumtaz, M. Qaiser Fatmi* and Muhammad J. Khan*

Volume 15 , Issue 2 , 2020

Page: [144 - 154] Pages: 11

DOI: 10.2174/1574893614666190923115032

Price: $65

Abstract

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of various renal diseases, including Chronic Kidney Diseases (CKD). CKD refers to the gradual loss of kidney function with the declining Glomerular Functional Rate (GFR).

Objective: This study focused on the regulatory mechanism of miRNA to control gene expression in CKD.

Methods: In this context, two lists of Differentially Expressed Genes (DEGs) were obtained; one from the three selected experiments by setting a cutoff p-value of <0.05 (List A), and one from a list of target genes of miRNAs (List B). Both lists were then compared to get a common dataset of 33 miRNAs, each had a set of DEGs i.e. both up-regulated and down-regulated genes (List C). These data were subjected to functional enrichment analysis, network illustration, and gene homology studies.

Results: This study confirmed the active participation of various miRNAs i.e. hsa -miR-15a-5p, hsa-miR-195-5p, hsa-miR-365-3p, hsa-miR-30a-5p, hsa-miR-124-3p, hsa-miR-200b-3p, and hsamiR- 429 in the dysregulation of genes involved in kidney development and function. Integrated analyses depicted that miRNAs modulated renal development, homeostasis, various metabolic processes, immune responses, and ion transport activities. Furthermore, homology studies of miRNA-mRNA hybrid highlighted the effect of partial complementary binding pattern on the regulation of genes by miRNA.

Conclusion: The study highlighted the great values of miRNAs as biomarkers in kidney diseases. In addition, the need for further investigations on miRNA-based studies is also commended in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.

Keywords: microRNA, gene expression, Chronic Kidney Diseases (CKD), Glomerular Functional Rate (GFR), dysregulation, biomarkers.

Graphical Abstract
[1]
Levey AS, Eckardt K-U, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005; 67(6): 2089-100.
[http://dx.doi.org/10.1111/j.1523-1755.2005.00365.x] [PMID: 15882252]
[2]
Schiffrin EL, Lipman ML, Mann JFE. Chronic kidney disease: effects on the cardiovascular system. Circulation 2007; 116(1): 85-97.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.678342] [PMID: 17606856]
[3]
Khella HWZ, Bakhet M, Lichner Z, Romaschin AD, Jewett MAS, Yousef GM. MicroRNAs in kidney disease: an emerging understanding. Am J Kidney Dis 2013; 61(5): 798-808.
[http://dx.doi.org/10.1053/j.ajkd.2012.09.018] [PMID: 23219107]
[4]
Neuen BL, Chadban SJ, Demaio AR, Johnson DW, Perkovic V. Chronic kidney disease and the global NCDs agenda. BMJ Glob Health 2017; 2(2): e000380
[http://dx.doi.org/10.1136/bmjgh-2017-000380] [PMID: 29225940]
[5]
Thompson S, Wiebe N, Padwal RS, et al. The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2019; 14(2): e0211032
[http://dx.doi.org/10.1371/journal.pone.0211032] [PMID: 30726242]
[6]
Balkau B, Metzger M, Andreelli F, et al. Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in people with type 2 diabetes and chronic kidney disease. The French Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) Study. Diabetes Metab 2019; 45(2): 175-83.
[http://dx.doi.org/10.1016/j.diabet.2018.03.007] [PMID: 29706470]
[7]
Jessani S, Bux R, Jafar TH. Prevalence, determinants, and management of chronic kidney disease in Karachi, Pakistan - a community based cross-sectional study. BMC Nephrol 2014; 15(1): 90.
[http://dx.doi.org/10.1186/1471-2369-15-90] [PMID: 24927636]
[8]
Sárközy M, Gáspár R, Zvara Á, et al. Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Sci Rep 2019; 9(1): 1302.
[http://dx.doi.org/10.1038/s41598-018-37690-5] [PMID: 30718600]
[9]
Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014; 42(Database issue): D68-73.
[http://dx.doi.org/10.1093/nar/gkt1181] [PMID: 24275495]
[10]
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): 843-54.
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[11]
Rudnicki M, Perco PD, Haene B, et al. Renal microRNA- and RNA-profiles in progressive chronic kidney disease. Eur J Clin Invest 2016; 46(3): 213-26.
[http://dx.doi.org/10.1111/eci.12585] [PMID: 26707063]
[12]
Hüttenhofer A, Mayer G. Circulating miRNAs as biomarkers of kidney disease. Clin Kidney J 2017; 10(1): 27-9.
[http://dx.doi.org/10.1093/ckj/sfw075] [PMID: 28639626]
[13]
Muendlein A, Geiger K, Leiherer A, et al. Correlation Between Circulating Micrornas and Chronic Kidney Disease in Patients With and Without Type 2 Diabetes. J Am Coll Cardiol 2018; 71(11): A1836.
[http://dx.doi.org/10.1016/S0735-1097(18)32377-5]
[14]
Bai M, Chen H, Ding D, et al. MicroRNA-214 promotes chronic kidney disease by disrupting mitochondrial oxidative phosphorylation. Kidney Int 2019; 95(6): 1389-404.
[http://dx.doi.org/10.1016/j.kint.2018.12.028] [PMID: 30955870]
[15]
Paradis P, Huo K-G, Richer C, et al. A2935 microRNA profiling in peripheral blood mononuclear cells from hypertensive patients with or without chronic kidney disease. J Hypertens 2018; 36: e21
[16]
Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res 2013; 41(Database issue): D991-5.
[http://dx.doi.org/10.1093/nar/gks1193] [PMID: 23193258]
[17]
Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 2015; 43(Database issue): D146-52.
[http://dx.doi.org/10.1093/nar/gku1104] [PMID: 25378301]
[18]
Zahra A, Rubab I, Malik S, Khan A, Khan MJ, Fatmi MQ. Meta-analysis of miRNAs and their involvement as biomarkers in oral cancers. BioMed Res Int 2018; 20188439820
[http://dx.doi.org/10.1155/2018/8439820] [PMID: 29516011]
[19]
Wang S, Zhang X, Hao F, et al. Reconstruction and functional annotation of P311 protein-protein interaction network reveals its new functions. Front Genet 2019; 10: 109.
[http://dx.doi.org/10.3389/fgene.2019.00109] [PMID: 30838032]
[20]
Wang Y, Lv K, Zhao M, et al. Expression profiles and functional annotation analysis of mRNAs in suprachiasmatic nucleus of Clock mutant mice. Gene 2018; 647: 107-14.
[http://dx.doi.org/10.1016/j.gene.2017.12.056] [PMID: 29307853]
[21]
Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[22]
Zuo Y, Gao Y, Su G, et al. Irregular transcriptome reprogramming probably caused embryo developmental failure of interspecies nuclear transfer between the Przewalski ’ s gazelle and the bovine 2014; 1-14.
[23]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498-504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[24]
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011; 39: D152-7.
[25]
Kruger J, Rehmsmeier M. RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 2006; 34(Web Server): W451-4.
[http://dx.doi.org/10.1093/nar/gkl243]
[26]
Xie Y, Jia Y, Cuihua X, Hu F, Xue M, Xue Y. Urinary exosomal microRNA profiling in incipient type 2 diabetic kidney disease. J Diabetes Res 2017; 2017: 6978984
[http://dx.doi.org/10.1155/2017/6978984] [PMID: 29038788]
[27]
Wei Q, Mi QS, Dong Z. The regulation and function of microRNAs in kidney diseases. IUBMB Life 2013; 65(7): 602-14.
[http://dx.doi.org/10.1002/iub.1174] [PMID: 23794512]
[28]
Pavkovic M, Vaidya VS. MicroRNAs and drug-induced kidney injury. Pharmacol Ther 2016; 163: 48-57.
[http://dx.doi.org/10.1016/j.pharmthera.2016.03.016] [PMID: 27126472]
[29]
Xie JX, Fan X, Drummond CA, et al. MicroRNA profiling in kidney disease: Plasma versus plasma-derived exosomes. Gene 2017; 627: 1-8.
[http://dx.doi.org/10.1016/j.gene.2017.06.003] [PMID: 28587849]
[30]
Zununi Vahed S, Poursadegh Zonouzi A, Mahmoodpoor F, Samadi N, Ardalan M, Omidi Y. Circulating miR-150, miR-192, miR-200b, and miR-423-3p as non-invasive biomarkers of chronic allograft dysfunction. Arch Med Res 2017; 48(1): 96-104.
[http://dx.doi.org/10.1016/j.arcmed.2017.03.004] [PMID: 28577875]
[31]
Ichii O, Otsuka S, Ohta H, Yabuki A, Horino T, Kon Y. MicroRNA expression profiling of cat and dog kidneys. Res Vet Sci 2014; 96(2): 299-303.
[http://dx.doi.org/10.1016/j.rvsc.2014.01.003] [PMID: 24530019]
[32]
Szeto CC, Ching-Ha KB, Ka-Bik L, et al. Micro-RNA expression in the urinary sediment of patients with chronic kidney diseases. Dis Markers 2012; 33(3): 137-44.
[http://dx.doi.org/10.1155/2012/842764] [PMID: 22960330]
[33]
Kiriakidou M, Nelson PT, Kouranov A, et al. A combined computational-experimental approach predicts human microRNA targets. Genes Dev 2004; 18(10): 1165-78.
[http://dx.doi.org/10.1101/gad.1184704] [PMID: 15131085]
[34]
Sun Y, Koo S, White N, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 2004; 32(22): e188-8.
[http://dx.doi.org/10.1093/nar/gnh186] [PMID: 15616155]
[35]
Chin LJ, Slack FJ. A truth serum for cancer--microRNAs have major potential as cancer biomarkers. Cell Res 2008; 18(10): 983-4.
[http://dx.doi.org/10.1038/cr.2008.290] [PMID: 18833286]
[36]
Gurtan AM, Sharp PA. The role of miRNAs in regulating gene expression networks. J Mol Biol 2013; 425(19): 3582-600.
[http://dx.doi.org/10.1016/j.jmb.2013.03.007] [PMID: 23500488]
[37]
Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA 2003; 9(1): 112-23.
[http://dx.doi.org/10.1261/rna.2780503] [PMID: 12554881]
[38]
Neal CS, Michael MZ, Pimlott LK, Yong TY, Li JYZ, Gleadle JM. Circulating microRNA expression is reduced in chronic kidney disease. Nephrol Dial Transplant 2011; 26(11): 3794-802.
[http://dx.doi.org/10.1093/ndt/gfr485] [PMID: 21891774]
[39]
Muralidharan J, Ramezani A, Hubal M, et al. Extracellular microRNA signature in chronic kidney disease. Am J Physiol Renal Physiol 2017; 312(6): F982-91.
[http://dx.doi.org/10.1152/ajprenal.00569.2016] [PMID: 28077372]
[40]
Kiriakidou M, Nelson P, Lamprinaki S, Sharma A, Mourelatos Z. Detection of MicroRNAs and assays to monitor MicroRNA activities in vivo and in vitro 2005; 309: 295-310.
[http://dx.doi.org/10.1385/1-59259-935-4:295]
[41]
Wang G, Kwan BC-H, Lai FM-M, et al. Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am J Hypertens 2010; 23(1): 78-84.
[http://dx.doi.org/10.1038/ajh.2009.208]] [PMID: 19910931]
[42]
Chandrasekaran K, Karolina DS, Sepramaniam S, et al. Role of microRNAs in kidney homeostasis and disease. Kidney Int 2012; 81(7): 617-27.
[http://dx.doi.org/10.1038/ki.2011.448] [PMID: 22237749]
[43]
Hauser AB, Stinghen AEM, Kato S, et al. Characteristics and causes of immune dysfunction related to uremia and dialysis. Perit Dial Int 2008; 28(Suppl. 3): S183-7.
[PMID: 18552253]
[44]
Gobal F, Deshmukh A, Shah S, Mehta JL. Triad of metabolic syndrome, chronic kidney disease, and coronary heart disease with a focus on microalbuminuria death by overeating. J Am Coll Cardiol 2011; 57(23): 2303-8.
[http://dx.doi.org/10.1016/j.jacc.2011.02.027] [PMID: 21636030]
[45]
Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics 2014; 2014970607
[http://dx.doi.org/10.1155/2014/970607] [PMID: 25180174]
[46]
Al-Chaqmaqchi HAM, Moshfegh A, Dadfar E, et al. Activation of Wnt/β-catenin pathway in monocytes derived from chronic kidney disease patients. PLoS One 2013; 8(7): e68937
[http://dx.doi.org/10.1371/journal.pone.0068937] [PMID: 23935909]
[47]
Scherer A, Günther OP, Balshaw RF, et al. Alteration of human blood cell transcriptome in uremia. BMC Med Genomics 2013; 6(1): 23.
[http://dx.doi.org/10.1186/1755-8794-6-23] [PMID: 23809614]
[48]
Zaza G, Granata S, Rascio F, et al. A specific immune transcriptomic profile discriminates chronic kidney disease patients in predialysis from hemodialyzed patients. BMC Med Genomics 2013; 6(1): 17.
[http://dx.doi.org/10.1186/1755-8794-6-17] [PMID: 23663527]

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