Generic placeholder image

Current Pediatric Reviews

Author(s): Jayasree Nair* and Akhil Maheshwari

DOI: 10.2174/1573396317666211102093646

DownloadDownload PDF Flyer Cite As
Non-coding RNAs in Necrotizing Enterocolitis- A New Frontier?

Page: [25 - 32] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

With the recognition that only 2% of the human genome encodes for a protein, a large part of the “non-coding” portion is now being evaluated for a regulatory role in cellular processes. These non-coding RNAs (ncRNAs) are subdivided based on the size of the nucleotide transcript into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), but most of our attention has been focused on the role of microRNAs (miRNAs) in human health and disease. Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis affecting preterm infants, has a multifactorial, unclear etiopathogenesis, and we have no specific biomarkers for diagnosis or the impact of directed therapies. The information on ncRNAs, in general, and particularly in NEC, is limited. Increasing information from other inflammatory bowel disorders suggests that these transcripts may play an important role in intestinal inflammation. Here, we review ncRNAs for definitions, classifications, and possible roles in prematurity and NEC using some preliminary information from our studies and from an extensive literature search in multiple databases including PubMed, EMBASE, and Science Direct. miRNAs will be described in another manuscript in this series, hence in this manuscript we mainly focus on lncRNAs.

Keywords: Necrotizing enterocolitis, epigenetics, ncRNA, lncRNA, gut inflammation, miRNAs.

[1]
Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells. Nature 2012; 489(7414): 101-8.
[http://dx.doi.org/10.1038/nature11233] [PMID: 22955620]
[2]
Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12(12): 861-74.
[http://dx.doi.org/10.1038/nrg3074] [PMID: 22094949]
[3]
Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013; 19(2): 141-57.
[http://dx.doi.org/10.1261/rna.035667.112] [PMID: 23249747]
[4]
Feng J, Naiman DQ, Cooper B. Coding DNA repeated throughout intergenic regions of the Arabidopsis thaliana genome: Evolutionary footprints of RNA silencing. Mol Biosyst 2009; 5(12): 1679-87.
[http://dx.doi.org/10.1039/b903031j] [PMID: 19452047]
[5]
Okamura K, Lai EC. Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 2008; 9(9): 673-8.
[http://dx.doi.org/10.1038/nrm2479] [PMID: 18719707]
[6]
Kim VN. Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. Genes Dev 2006; 20(15): 1993-7.
[http://dx.doi.org/10.1101/gad.1456106] [PMID: 16882976]
[7]
Moazed D. Small RNAs in transcriptional gene silencing and genome defence. Nature 2009; 457(7228): 413-20.
[http://dx.doi.org/10.1038/nature07756] [PMID: 19158787]
[8]
Li LC, Okino ST, Zhao H, et al. Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci USA 2006; 103(46): 17337-42.
[http://dx.doi.org/10.1073/pnas.0607015103] [PMID: 17085592]
[9]
Alló M, Buggiano V, Fededa JP, et al. Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nat Struct Mol Biol 2009; 16(7): 717-24.
[http://dx.doi.org/10.1038/nsmb.1620] [PMID: 19543290]
[10]
Kapranov P, Cheng J, Dike S, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 2007; 316(5830): 1484-8.
[http://dx.doi.org/10.1126/science.1138341] [PMID: 17510325]
[11]
Jabandziev P, Bohosova J, Pinkasova T, Kunovsky L, Slaby O, Goel A. The emerging role of noncoding RNAs in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2020; 26(7): 985-93.
[http://dx.doi.org/10.1093/ibd/izaa009] [PMID: 32009179]
[12]
Batista PJ, Chang HY. Long noncoding RNAs: Cellular address codes in development and disease. Cell 2013; 152(6): 1298-307.
[http://dx.doi.org/10.1016/j.cell.2013.02.012] [PMID: 23498938]
[13]
Yarani R, Mirza AH, Kaur S, Pociot F. The emerging role of lncRNAs in inflammatory bowel disease. Exp Mol Med 2018; 50(12): 1-14.
[http://dx.doi.org/10.1038/s12276-018-0188-9] [PMID: 30523244]
[14]
Beermann J, Piccoli MT, Viereck J, Thum T. Non-coding RNAs in development and disease: Background, mechanisms, and therapeutic approaches. Physiol Rev 2016; 96(4): 1297-325.
[http://dx.doi.org/10.1152/physrev.00041.2015] [PMID: 27535639]
[15]
Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA. Nat Rev Mol Cell Biol 2018; 19(3): 143-57.
[http://dx.doi.org/10.1038/nrm.2017.104] [PMID: 29138516]
[16]
Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 2010; 142(3): 409-19.
[http://dx.doi.org/10.1016/j.cell.2010.06.040] [PMID: 20673990]
[17]
Goodrich JA, Kugel JF. Non-coding-RNA regulators of RNA polymerase II transcription. Nat Rev Mol Cell Biol 2006; 7(8): 612-6.
[http://dx.doi.org/10.1038/nrm1946] [PMID: 16723972]
[18]
Pennacchio LA, Ahituv N, Moses AM, et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006; 444(7118): 499-502.
[http://dx.doi.org/10.1038/nature05295] [PMID: 17086198]
[19]
Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 2006; 20(11): 1470-84.
[http://dx.doi.org/10.1101/gad.1416106] [PMID: 16705037]
[20]
Luo S, Lu JY, Liu L, et al. Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell 2016; 18(5): 637-52.
[http://dx.doi.org/10.1016/j.stem.2016.01.024] [PMID: 26996597]
[21]
Fatica A, Bozzoni I. Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet 2014; 15(1): 7-21.
[http://dx.doi.org/10.1038/nrg3606] [PMID: 24296535]
[22]
Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 2016; 17(1): 47-62.
[http://dx.doi.org/10.1038/nrg.2015.10] [PMID: 26666209]
[23]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[24]
Yoon JH, Abdelmohsen K, Gorospe M. Posttranscriptional gene regulation by long noncoding RNA. J Mol Biol 2013; 425(19): 3723-30.
[http://dx.doi.org/10.1016/j.jmb.2012.11.024] [PMID: 23178169]
[25]
Kwek KY, Murphy S, Furger A, et al. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol 2002; 9(11): 800-5.
[http://dx.doi.org/10.1038/nsb862] [PMID: 12389039]
[26]
Mariner PD, Walters RD, Espinoza CA, et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell 2008; 29(4): 499-509.
[http://dx.doi.org/10.1016/j.molcel.2007.12.013] [PMID: 18313387]
[27]
Pauler FM, Koerner MV, Barlow DP. Silencing by imprinted noncoding RNAs: Is transcription the answer? Trends Genet 2007; 23(6): 284-92.
[http://dx.doi.org/10.1016/j.tig.2007.03.018] [PMID: 17445943]
[28]
Czech B, Malone CD, Zhou R, et al. An endogenous small interfering RNA pathway in Drosophila. Nature 2008; 453(7196): 798-802.
[http://dx.doi.org/10.1038/nature07007] [PMID: 18463631]
[29]
Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 2007; 318(5851): 798-801.
[http://dx.doi.org/10.1126/science.1147182] [PMID: 17916692]
[30]
Heskett MB, Smith LG, Spellman P, Thayer MJ. Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6. RNA 2020; 26(6): 724-38.
[http://dx.doi.org/10.1261/rna.073114.119] [PMID: 32144193]
[31]
Xiao L, Wu J, Wang JY, et al. Long noncoding RNA uc.173 promotes renewal of the intestinal mucosa by inducing degradation of microRNA 195. Gastroenterology 2018; 154(3): 599-611.
[http://dx.doi.org/10.1053/j.gastro.2017.10.009] [PMID: 29042220]
[32]
Feuerhahn S, Iglesias N, Panza A, Porro A, Lingner J. TERRA biogenesis, turnover and implications for function. FEBS Lett 2010; 584(17): 3812-8.
[http://dx.doi.org/10.1016/j.febslet.2010.07.032] [PMID: 20655916]
[33]
Nam JW, Choi SW, You BH. Incredible RNA: Dual functions of coding and noncoding. Mol Cells 2016; 39(5): 367-74.
[http://dx.doi.org/10.14348/molcells.2016.0039] [PMID: 27137091]
[34]
Milligan MJ, Lipovich L. Pseudogene-derived lncRNAs: Emerging regulators of gene expression. Front Genet 2015; 5: 476.
[http://dx.doi.org/10.3389/fgene.2014.00476] [PMID: 25699073]
[35]
van Dijk M, Thulluru HK, Mulders J, et al. HELLP babies link a novel lincRNA to the trophoblast cell cycle. J Clin Invest 2012; 122(11): 4003-11.
[http://dx.doi.org/10.1172/JCI65171] [PMID: 23093777]
[36]
Yoffe L, Gilam A, Yaron O, et al. Early detection of preeclampsia using circulating small non-coding RNA. Sci Rep 2018; 8(1): 3401.
[http://dx.doi.org/10.1038/s41598-018-21604-6] [PMID: 29467498]
[37]
He X, He Y, Xi B, et al. LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis. PLoS One 2013; 8(11): e81437.
[http://dx.doi.org/10.1371/journal.pone.0081437] [PMID: 24312300]
[38]
Zou Y, Jiang Z, Yu X, et al. Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. PLoS One 2013; 8(11): e79598.
[http://dx.doi.org/10.1371/journal.pone.0079598] [PMID: 24223182]
[39]
Chen H, Meng T, Liu X, et al. Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. Int J Clin Exp Pathol 2015; 8(10): 12718-27.
[PMID: 26722461]
[40]
Long W, Rui C, Song X, et al. Distinct expression profiles of lncRNAs between early-onset preeclampsia and preterm controls. Clin Chim Acta 2016; 463: 193-9.
[http://dx.doi.org/10.1016/j.cca.2016.10.036] [PMID: 27816668]
[41]
Guo L, Choufani S, Ferreira J, et al. Altered gene expression and methylation of the human chromosome 11 imprinted region in Small for Gestational Age (SGA) placentae. Dev Biol 2008; 320(1): 79-91.
[http://dx.doi.org/10.1016/j.ydbio.2008.04.025] [PMID: 18550048]
[42]
Tseng JJ, Hsieh YT, Hsu SL, Chou MM. Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro. Mol Hum Reprod 2009; 15(11): 725-31.
[http://dx.doi.org/10.1093/molehr/gap071] [PMID: 19690017]
[43]
Clemson CM, Hutchinson JN, Sara SA, et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 2009; 33(6): 717-26.
[http://dx.doi.org/10.1016/j.molcel.2009.01.026] [PMID: 19217333]
[44]
Zuckerwise L, Li J, Lu L, et al. H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction. Oncotarget 2016; 7(25): 38398-407.
[http://dx.doi.org/10.18632/oncotarget.9534] [PMID: 27223264]
[45]
Gremlich S, Damnon F, Reymondin D, et al. The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development. Placenta 2014; 35(1): 44-9.
[http://dx.doi.org/10.1016/j.placenta.2013.11.003] [PMID: 24280234]
[46]
Zhang Y, Zou Y, Wang W, et al. Down-regulated long non-coding RNA MEG3 and its effect on promoting apoptosis and suppressing migration of trophoblast cells. J Cell Biochem 2015; 116(4): 542-50.
[http://dx.doi.org/10.1002/jcb.25004] [PMID: 25358633]
[47]
Wang JY, Cui YH, Xiao L, et al. Regulation of intestinal epithelial barrier function by long noncoding RNA uc.173 through interaction with microRNA 29b. Mol Cell Biol 2018; 38(13): e00010-18.
[http://dx.doi.org/10.1128/MCB.00010-18] [PMID: 29632078]
[48]
Zhu P, Wu J, Wang Y, et al. LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis. Nat Cell Biol 2018; 20(10): 1134-44.
[http://dx.doi.org/10.1038/s41556-018-0194-0] [PMID: 30224759]
[49]
Wang JY, Xiao L, Wang JY. Posttranscriptional regulation of intestinal epithelial integrity by noncoding RNAs. Wiley Interdiscip Rev RNA 2017; 8(2)
[http://dx.doi.org/10.1002/wrna.1399] [PMID: 27704722]
[50]
Zou T, Jaladanki SK, Liu L, et al. H19 long noncoding RNA regulates intestinal epithelial barrier function via microRNA 675 by interacting with RNA-binding protein HuR. Mol Cell Biol 2016; 36(9): 1332-41.
[http://dx.doi.org/10.1128/MCB.01030-15] [PMID: 26884465]
[51]
Su Z, Zhi X, Zhang Q, Yang L, Xu H, Xu Z. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier. FEBS Lett 2016; 590(9): 1354-64.
[http://dx.doi.org/10.1002/1873-3468.12171] [PMID: 27059301]
[52]
Xiao L, Rao JN, Cao S, et al. Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins. Mol Biol Cell 2016; 27(4): 617-26.
[http://dx.doi.org/10.1091/mbc.E15-10-0703] [PMID: 26680741]
[53]
Xiao L, Gorospe M, Wang JY. Long noncoding RNAs in intestinal epithelium homeostasis. Am J Physiol Cell Physiol 2019; 317(1): C93-C100.
[http://dx.doi.org/10.1152/ajpcell.00092.2019] [PMID: 31042423]
[54]
Pammi M, De Plaen IG, Maheshwari A. Recent advances in necrotizing enterocolitis research: Strategies for implementation in clinical practice. Clin Perinatol 2020; 47(2): 383-97.
[http://dx.doi.org/10.1016/j.clp.2020.02.011] [PMID: 32439118]
[55]
Nair J, Lakshminrusimha S. Role of NO and other vascular mediators in the etiopathogenesis of necrotizing enterocolitis. Front Biosci (Schol Ed) 2019; 11: 9-28.
[http://dx.doi.org/10.2741/s524] [PMID: 30844734]
[56]
Fiedler J, Breckwoldt K, Remmele CW, et al. Development of long noncoding RNA-based strategies to modulate tissue vascularization. J Am Coll Cardiol 2015; 66(18): 2005-15.
[http://dx.doi.org/10.1016/j.jacc.2015.07.081] [PMID: 26516004]
[57]
He C, Ding JW, Li S, et al. The role of long intergenic noncoding RNA p21 in vascular endothelial cells. DNA Cell Biol 2015; 34(11): 677-83.
[http://dx.doi.org/10.1089/dna.2015.2966] [PMID: 26273737]
[58]
Boeckel JN, Jaé N, Heumüller AW, et al. Identification and characterization of hypoxia-regulated endothelial circular RNA. Circ Res 2015; 117(10): 884-90.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306319] [PMID: 26377962]
[59]
Chen W, Yan X, Tian T, et al. Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis. Mol Med Rep 2020; 22(1): 423-35.
[PMID: 32319640]
[60]
Xu Y, Liu Y, Xie H, et al. Profile analysis reveals endogenous RNAs regulate necrotizing enterocolitis progression. Biomed Pharmacother 2020; 125: 109975.
[http://dx.doi.org/10.1016/j.biopha.2020.109975] [PMID: 32036223]
[61]
Ray K. IBD. Understanding gut microbiota in new-onset Crohn’s disease. Nat Rev Gastroenterol Hepatol 2014; 11(5): 268.
[http://dx.doi.org/10.1038/nrgastro.2014.45] [PMID: 24662277]
[62]
Liang L, Ai L, Qian J, Fang JY, Xu J. Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes. Sci Rep 2015; 5: 11763.
[http://dx.doi.org/10.1038/srep11763] [PMID: 26123364]
[63]
Dempsey J, Zhang A, Cui JY. Coordinate regulation of long non-coding RNAs and protein-coding genes in germ-free mice. BMC Genomics 2018; 19(1): 834.
[http://dx.doi.org/10.1186/s12864-018-5235-3] [PMID: 30463508]
[64]
Mirza AH, Berthelsen CH, Seemann SE, et al. Transcriptomic landscape of lncRNAs in inflammatory bowel disease. Genome Med 2015; 7(1): 39.
[http://dx.doi.org/10.1186/s13073-015-0162-2] [PMID: 25991924]
[65]
Han J, Li Y, Zhang B, Liu H, Wu M, Zhang X. lncRNA TUG1 regulates ulcerative colitis through miR-142-5p/SOCS1 axis. Microb Pathog 2020; 143: 104139.
[http://dx.doi.org/10.1016/j.micpath.2020.104139] [PMID: 32173492]
[66]
Chen D, Liu J, Zhao HY, Chen YP, Xiang Z, Jin X. Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn’s disease. World J Gastroenterol 2016; 22(19): 4716-31.
[http://dx.doi.org/10.3748/wjg.v22.i19.4716] [PMID: 27217703]
[67]
Qian XX, Peng JC, Xu AT, et al. Noncoding Transcribed Ultraconserved Region (T-UCR) uc.261 participates in intestinal mucosa barrier damage in Crohn’s disease. Inflamm Bowel Dis 2016; 22(12): 2840-52.
[http://dx.doi.org/10.1097/MIB.0000000000000945] [PMID: 27846191]