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Short Communication

The Core Human MicroRNAs Regulated by Toxoplasma gondii

Author(s): Neelam Antil, Mohammad Arefian, Mrudula Kinarulla Kandiyil, Kriti Awasthi, Thottethodi Subrahmanya Keshava Prasad* and Rajesh Raju*

Volume 11, Issue 2, 2022

Published on: 15 August, 2022

Page: [163 - 174] Pages: 12

DOI: 10.2174/2211536611666220428130250

Price: $65

Abstract

Background: Toxoplasma gondii (T. gondii) is an intracellular zoonotic protozoan parasite known to effectively modulate the host system for its survival. A large number of microRNAs (miRNAs) regulated by different strains of T. gondii in diverse types of host cells/tissues/organs have been reported across multiple studies.

Objective: We aimed to decipher the complexity of T. gondii regulated spectrum of miRNAs to derive a set of core miRNAs central to different strains of T. gondii infection in diverse human cell lines.

Methods: We first assembled miRNAs hat are regulated by T. gondii altered across the various assortment of infections and time points of T. gondii infection in multiple cell types. For these assembled datasets, we employed specific criteria to filter the core miRNAs regulated by T. gondii. Subsequently, accounting for the spectrum of miRNA-mRNA target combinations, we applied a novel confidence criterion to extract their core experimentally-validated mRNA targets in human cell systems.

Results: This analysis resulted in the extraction of 74 core differentially regulated miRNAs and their 319 high-confidence mRNA targets. Based on these core miRNA-mRNA pairs, we derived the central biological processes perturbed by T. gondii in diverse human cell systems. Further, our analysis also resulted in the identification of novel autocrine/paracrine signalling factors that could be associated with host response modulated by T. gondii.

Conclusion: The current analysis derived a set of core miRNAs, their targets, and associated biological processes fine-tuned by T. gondii for its survival within the invaded cells.

Keywords: Apicomplexan parasites, toxoplasmosis, microRNA, bioinformatics, miRNA-mRNA interaction, regulatory network.

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Graphical Abstract

[1]
Saadatnia, G.; Golkar, M. A review on human toxoplasmosis. Scand. J. Infect. Dis., 2012, 44(11), 805-814.
[http://dx.doi.org/10.3109/00365548.2012.693197] [PMID: 22831461]
[2]
Montoya, J.G.; Liesenfeld, O. Toxoplasmosis. Lancet, 2004, 363(9425), 1965-1976.
[http://dx.doi.org/10.1016/S0140-6736(04)16412-X] [PMID: 15194258]
[3]
Antil, N.; Kumar, M.; Behera, S.K. Unraveling Toxoplasma gondii GT1 strain virulence and new protein-coding genes with proteogenomic analyses. OMICS, 2021, 25(9), 591-604.
[http://dx.doi.org/10.1089/omi.2021.0082] [PMID: 34468217]
[4]
Khan, K.; Khan, W. Congenital toxoplasmosis: An overview of the neurological and ocular manifestations. Parasitol. Int., 2018, 67(6), 715-721.
[http://dx.doi.org/10.1016/j.parint.2018.07.004] [PMID: 30041005]
[5]
Oz, H.S. Maternal and congenital toxoplasmosis, currently available and novel therapies in horizon. Front. Microbiol., 2014, 5, 385.
[http://dx.doi.org/10.3389/fmicb.2014.00385] [PMID: 25104952]
[6]
Boothroyd, J.C.; Grigg, M.E. Population biology of Toxoplasma gondii and its relevance to human infection: Do different strains cause different disease? Curr. Opin. Microbiol., 2002, 5(4), 438-442.
[http://dx.doi.org/10.1016/S1369-5274(02)00349-1] [PMID: 12160866]
[7]
Dardé, M.L. Toxoplasma gondii, “new” genotypes and virulence. Parasite, 2008, 15(3), 366-371.
[http://dx.doi.org/10.1051/parasite/2008153366] [PMID: 18814708]
[8]
Xiao, J.; Yolken, R.H. Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases. Acta Physiol. (Oxf.), 2015, 213(4), 828-845.
[http://dx.doi.org/10.1111/apha.12458] [PMID: 25600911]
[9]
Li, M.; Mo, X.W.; Wang, L. Phylogeny and virulence divergency analyses of Toxoplasma gondii isolates from China. Parasit. Vectors, 2014, 7(1), 133.
[http://dx.doi.org/10.1186/1756-3305-7-133] [PMID: 24678633]
[10]
Heussler, V.T.; Küenzi, P.; Rottenberg, S. Inhibition of apoptosis by intracellular protozoan parasites. Int. J. Parasitol., 2001, 31(11), 1166-1176.
[http://dx.doi.org/10.1016/S0020-7519(01)00271-5] [PMID: 11563357]
[11]
Blader, I.J.; Koshy, A.A. Toxoplasma gondii development of its replicative niche: In its host cell and beyond. Eukaryot. Cell, 2014, 13(8), 965-976.
[http://dx.doi.org/10.1128/EC.00081-14] [PMID: 24951442]
[12]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[13]
Hombach, S.; Kretz, M. Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma. Mol. Med. Rep., 2016, 17(5), 6935-6941.
[14]
Mortensen, R.D.; Serra, M.; Steitz, J.A.; Vasudevan, S. Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc. Natl. Acad. Sci. USA, 2011, 108(20), 8281-8286.
[http://dx.doi.org/10.1073/pnas.1105401108] [PMID: 21536868]
[15]
Vasudevan, S.; Tong, Y.; Steitz, J.A. Switching from repression to activation: MicroRNAs can up-regulate translation. Science, 2007, 318(5858), 1931-1934.
[http://dx.doi.org/10.1126/science.1149460] [PMID: 18048652]
[16]
Zeiner, G.M.; Norman, K.L.; Thomson, J.M.; Hammond, S.M.; Boothroyd, J.C. Toxoplasma gondii infection specifically increases the levels of key host microRNAs. PLoS One, 2010, 5(1), e8742.
[http://dx.doi.org/10.1371/journal.pone.0008742] [PMID: 20090903]
[17]
Franco, M.; Shastri, A.J.; Boothroyd, J.C. Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates. Eukaryot. Cell, 2014, 13(4), 483-493.
[http://dx.doi.org/10.1128/EC.00316-13] [PMID: 24532536]
[18]
Jia, B.; Chang, Z.; Wei, X. Plasma microRNAs are promising novel biomarkers for the early detection of Toxoplasma gondii infection. Parasit. Vectors, 2014, 7(1), 433.
[http://dx.doi.org/10.1186/1756-3305-7-433] [PMID: 25199527]
[19]
Cannella, D.; Brenier-Pinchart, M-P.; Braun, L. miR-146a and miR-155 delineate a MicroRNA fingerprint associated with Toxoplasma persistence in the host brain. Cell Rep., 2014, 6(5), 928-937.
[http://dx.doi.org/10.1016/j.celrep.2014.02.002] [PMID: 24582962]
[20]
Rezaei, F.; Daryani, A.; Sharifi, M. miR-20a inhibition using Locked Nucleic Acid (LNA) technology and its effects on apoptosis of human macrophages infected by Toxoplasma gondii RH strain. Microb. Pathog., 2018, 121, 269-276.
[http://dx.doi.org/10.1016/j.micpath.2018.05.030] [PMID: 29800695]
[21]
Cai, Y.; Chen, H.; Mo, X. Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17-92-Bim pathway in macrophages. Cell. Signal., 2014, 26(6), 1204-1212.
[http://dx.doi.org/10.1016/j.cellsig.2014.02.013] [PMID: 24583285]
[22]
Ngô, H.M.; Zhou, Y.; Lorenzi, H. Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer. Sci. Rep., 2017, 7(1), 11496.
[http://dx.doi.org/10.1038/s41598-017-10675-6] [PMID: 28904337]
[23]
Li, D.L.; Zou, W.H.; Deng, S.Q.; Peng, H.J. Analysis of the differential exosomal miRNAs of DC2.4 dendritic cells induced by Toxoplasma gondii Infection. Int. J. Mol. Sci., 2019, 20(21), 5506.
[http://dx.doi.org/10.3390/ijms20215506] [PMID: 31694199]
[24]
Kim, M.J.; Jung, B.K.; Cho, J. Exosomes secreted by Toxoplasma gondii-infected L6 cells: Their effects on host cell proliferation and cell cycle changes. Korean J. Parasitol., 2016, 54(2), 147-154.
[http://dx.doi.org/10.3347/kjp.2016.54.2.147] [PMID: 27180572]
[25]
Medina, L.; Castillo, C.; Liempi, A. Trypanosoma cruzi and Toxoplasma gondii induce a differential microRNA profile in human placental explants. Front. Immunol., 2020, 11, 595250.
[http://dx.doi.org/10.3389/fimmu.2020.595250] [PMID: 33240284]
[26]
Xiao, J.; Li, Y.; Prandovszky, E. MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway. Neuroscience, 2014, 268, 128-138.
[http://dx.doi.org/10.1016/j.neuroscience.2014.03.015] [PMID: 24657774]
[27]
He, J.J.; Ma, J.; Wang, J.L.; Xu, M.J.; Zhu, X.Q. Analysis of miRNA expression profiling in mouse spleen affected by acute Toxoplasma gondii infection. Infect. Genet. Evol., 2016, 37, 137-142.
[http://dx.doi.org/10.1016/j.meegid.2015.11.005] [PMID: 26569573]
[28]
Lee, H.M.; Kim, T.S.; Jo, E.K. MiR-146 and miR-125 in the regulation of innate immunity and inflammation. BMB Rep., 2016, 49(6), 311-318.
[http://dx.doi.org/10.5483/BMBRep.2016.49.6.056] [PMID: 26996343]
[29]
Cui, J.G.; Li, Y.Y.; Zhao, Y.; Bhattacharjee, S.; Lukiw, W.J. Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease. J. Biol. Chem., 2010, 285(50), 38951-38960.
[http://dx.doi.org/10.1074/jbc.M110.178848] [PMID: 20937840]
[30]
Park, H.; Huang, X.; Lu, C.; Cairo, M.S.; Zhou, X. MicroRNA-146a and microRNA-146b regulate human dendritic cell apoptosis and cytokine production by targeting TRAF6 and IRAK1 proteins. J. Biol. Chem., 2015, 290(5), 2831-2841.
[http://dx.doi.org/10.1074/jbc.M114.591420] [PMID: 25505246]
[31]
Cai, Y.; Chen, H.; Jin, L.; You, Y.; Shen, J. STAT3-dependent transactivation of miRNA genes following Toxoplasma gondii infection in macrophage. Parasit. Vectors, 2013, 6(1), 356.
[http://dx.doi.org/10.1186/1756-3305-6-356] [PMID: 24341525]
[32]
Baek, D.; Villén, J.; Shin, C.; Camargo, F.D.; Gygi, S.P.; Bartel, D.P. The impact of microRNAs on protein output. Nature, 2008, 455(7209), 64-71.
[http://dx.doi.org/10.1038/nature07242] [PMID: 18668037]
[33]
Revikumar, A.; Kashyap, V.; Palollathil, A. Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines. J. Cell Commun. Signal., 2022, 16(2), 129-135.
[PMID: 34309794]
[34]
Karagkouni, D.; Paraskevopoulou, M.D.; Chatzopoulos, S. DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Res., 2018, 46(D1), D239-D245.
[http://dx.doi.org/10.1093/nar/gkx1141] [PMID: 29156006]
[35]
Raudvere, U.; Kolberg, L.; Kuzmin, I. g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res., 2019, 47(W1), W191-8.
[http://dx.doi.org/10.1093/nar/gkz369] [PMID: 31066453]
[36]
Seifert, E. OriginPro 9.1: Scientific data analysis and graphing software-software review. J. Chem. Inf. Model., 2014, 54(5), 1552.
[http://dx.doi.org/10.1021/ci500161d] [PMID: 24702057]
[37]
Bastian, M.; Heymann, S.; Jacomy, M. IL-27 alleviates airway remodeling in a mouse model of asthma via PI3K/Akt pathway. Exp. Lung Res., 2009, 46(3-4), 98-108.
[38]
Clegg, J.C.; Wilson, S.M.; Oram, J.D. Nucleotide sequence of the S RNA of Lassa virus (Nigerian strain) and comparative analysis of arenavirus gene products. Virus Res., 1991, 18(2-3), 151-164.
[http://dx.doi.org/10.1016/0168-1702(91)90015-N] [PMID: 2042397]
[39]
Hashimoto, Y.; Akiyama, Y.; Yuasa, Y. Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer. PLoS One, 2013, 8(5), e62589.
[http://dx.doi.org/10.1371/journal.pone.0062589] [PMID: 23667495]
[40]
Gubbels, M.J.; White, M.; Szatanek, T. The cell cycle and Toxoplasma gondii cell division: Tightly knit or loosely stitched? Int. J. Parasitol., 2008, 38(12), 1343-1358.
[http://dx.doi.org/10.1016/j.ijpara.2008.06.004] [PMID: 18703066]
[41]
Spear, W.; Chan, D.; Coppens, I.; Johnson, R.S.; Giaccia, A.; Blader, I.J. The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels. Cell. Microbiol., 2006, 8(2), 339-352.
[http://dx.doi.org/10.1111/j.1462-5822.2005.00628.x] [PMID: 16441443]
[42]
Kanehisa, M.; Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]
[43]
Jassal, B.; Matthews, L.; Viteri, G. The reactome pathway knowledgebase. Nucleic Acids Res., 2020, 48(D1), D498-D503.
[PMID: 31691815]
[44]
Coppens, I.; Sinai, A.P.; Joiner, K.A. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition. J. Cell Biol., 2000, 149(1), 167-180.
[http://dx.doi.org/10.1083/jcb.149.1.167] [PMID: 10747095]
[45]
Portugal, L.R.; Fernandes, L.R.; Pietra Pedroso, V.S.; Santiago, H.C.; Gazzinelli, R.T.; Alvarez-Leite, J.I. Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection. Microbes Infect., 2008, 10(3), 276-284.
[http://dx.doi.org/10.1016/j.micinf.2007.12.001] [PMID: 18316222]
[46]
Sanchez, Y.; de Dios Rosado, J.; Vega, L. MicroRNA–21 as a novel biomarker in diagnosis and response to therapy in asthmatic children. Mol. Immunol., 2010, 71, 107-4.
[http://dx.doi.org/10.1155/2010/505694]
[47]
Wagage, S.; Harms Pritchard, G.; Dawson, L.; Buza, E.L.; Sonnenberg, G.F.; Hunter, C.A. The group 3 innate lymphoid cell defect in aryl hydrocarbon receptor deficient mice is associated with T cell hyperactivation during intestinal infection. PLoS One, 2015, 10(5), e0128335.
[http://dx.doi.org/10.1371/journal.pone.0128335] [PMID: 26010337]
[48]
O’Brien, C.A.; Batista, S.J.; Still, K.M.; Harris, T.H. IL-10 and ICOS differentially regulate T cell responses in the brain during chronic Toxoplasma gondii infection. J. Immunol., 2019, 202(6), 1755-1766.
[http://dx.doi.org/10.4049/jimmunol.1801229] [PMID: 30718297]
[49]
Mathur, G.; George, A.E.; Sen, P. Paediatric choroidal neovascular membrane secondary to toxoplasmosis treated successfully with anti-vascular endothelial growth factor. Oman J. Ophthalmol., 2014, 7(3), 141-143.
[http://dx.doi.org/10.4103/0974-620X.142598] [PMID: 25378880]
[50]
Wiertz, K.; De Visser, L.; Rijkers, G.; De Groot-Mijnes, J.; Los, L.; Rothova, A. Intraocular and serum levels of vascular endothelial growth factor in acute retinal necrosis and ocular toxoplasmosis. Retina, 2010, 30(10), 1734-1738.
[http://dx.doi.org/10.1097/IAE.0b013e3181dde70b] [PMID: 20706172]
[51]
Hu, W.; Feng, Z.; Levine, A.J. The regulation of multiple p53 stress responses is mediated through MDM2. Genes Cancer, 2012, 3(3-4), 199-208.
[http://dx.doi.org/10.1177/1947601912454734] [PMID: 23150753]
[52]
Wade, M.; Wahl, G.M. Targeting Mdm2 and Mdmx in cancer therapy: Better living through medicinal chemistry? Mol. Cancer Res., 2009, 7(1), 1-11.
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0423] [PMID: 19147532]
[53]
Jiang, H.; Zhai, T.; Yu, Y. Delayed IL-12 production by macrophages during Toxoplasma gondii infection is regulated by miR-187. Parasitol. Res., 2020, 119(3), 1023-1033.
[http://dx.doi.org/10.1007/s00436-019-06588-0] [PMID: 32065264]
[54]
Seok, J.K.; Lee, S.H.; Kim, M.J.; Lee, Y.M. MicroRNA-382 induced by HIF-1α is an angiogenic miR targeting the tumor suppressor phosphatase and tensin homolog. Nucleic Acids Res., 2014, 42(12), 8062-8072.
[http://dx.doi.org/10.1093/nar/gku515] [PMID: 24914051]
[55]
Lis, A.; Wiley, M.; Vaughan, J.; Gray, P.C.; Blader, I.J. The activin receptor, activin-like kinase 4, mediates Toxoplasma gondii activation of hypoxia inducible factor-1. Front. Cell. Infect. Microbiol., 2019, 9, 36.
[http://dx.doi.org/10.3389/fcimb.2019.00036] [PMID: 30891432]

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