Newborn

Register      Login

VOLUME 1 , ISSUE 1 ( January-March, 2022 ) > List of Articles

REVIEW ARTICLE

Non-coding RNAs in Neonatal Necrotizing Enterocolitis

Keyur Donda, Benjamin A Torres, Akhil Maheshwari

Keywords : Genetic predisposition, Intestinal inflammation, Necrotizing enterocolitis, Neonates, Non-coding RNA, Spontaneous intestinal perforation

Citation Information : Donda K, Torres BA, Maheshwari A. Non-coding RNAs in Neonatal Necrotizing Enterocolitis. 2022; 1 (1):120-130.

DOI: 10.5005/jp-journals-11002-0012

License: CC BY-NC 4.0

Published Online: 31-03-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

The incomplete understanding of the etiopathogenesis of necrotizing enterocolitis (NEC) contributes to the lack of timely diagnosis and limited therapeutic options. Non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression in various pathways that can modulate various physiological and pathological processes. Despite several studies revealing the role of ncRNAs in intestinal inflammatory diseases in adults, these remain largely unexplored in NEC. In this article, we review the information on ncRNAs that have been specifically identified in NEC or have been noted in other inflammatory bowel disorders that share some of the histopathological abnormalities seen frequently in NEC. We have assimilated the most current research findings on ncRNAs in intestinal diseases. This is an attempt to explore a novel field that has immense potential for future translational and clinical research in preventing, detecting, and treating NEC.


HTML PDF Share
  1. Denning PW, Maheshwari A. Necrotizing enterocolitis: hope on the horizon. Clin Perinatol 2013;40(1):xvii–xix. DOI: 10.1016/j.clp.2013.01.001.
  2. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011;12(12):861–874. DOI: 10.1038/nrg3074.
  3. Boivin V, Faucher-Giguère L, Scott M, et al. The cellular landscape of mid-size noncoding RNA. WIREs RNA 2019;10(4):e1530. DOI: 10.1002/wrna.1530.
  4. Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013;19(2):141–157. DOI: 10.1261/rna.035667.112.
  5. 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):1679–1687. DOI: 10.1039/b903031j.
  6. Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 2015;16(7):421–433. DOI: 10.1038/nrg3965.
  7. Ozsolak F, Poling LL, Wang Z, et al. Chromatin structure analyses identify miRNA promoters. Genes Dev 2008;22(22):3172–3183. DOI: 10.1101/gad.1706508.
  8. Yi R, Qin Y, Macara IG, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003;17(24):3011–3016. DOI: 10.1101/gad.1158803.
  9. Gregory RI, Chendrimada TP, Cooch N, et al. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005;123(4):631–640. DOI: 10.1016/j.cell.2005.10.022.
  10. Denli AM, Tops BB, Plasterk RH, et al. Processing of primary microRNAs by the Microprocessor complex. Nature 2004;432(7014):231–235. DOI: 10.1038/nature03049.
  11. Peterson SM, Thompson JA, Ufkin ML, et al. Common features of microRNA target prediction tools. Front Genet 2014;5:23. DOI: 10.3389/fgene.2014.00023.
  12. Lewis BP, Shih IH, Jones-Rhoades MW, et al. Prediction of mammalian microRNA targets. Cell 2003;115(7):787–798. DOI: 10.1016/s0092-8674(03)01018-3.
  13. Friedman RC, Farh KKH, Burge CB, et al. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009;19(1):92–105. DOI: 10.1101/gr.082701.108.
  14. Kondkar AA, Abu-Amero KK. Utility of circulating microRNAs as clinical biomarkers for cardiovascular diseases. Biomed Res Int 2015;2015:821823. DOI: 10.1155/2015/821823.
  15. Guo B, Li D, Du L, et al. piRNAs: biogenesis and their potential roles in cancer. Cancer Metastasis Rev 2020;39(2):567–575. DOI: 10.1007/s10555-020-09863-0.
  16. Hirakata S, Ishizu H, Fujita A, et al. Requirements for multivalent Yb body assembly in transposon silencing in Drosophila. EMBO reports 2019;20(7):e47708. DOI: 10.15252/embr.201947708.
  17. Théron E, Maupetit-Mehouas S, Pouchin P, et al. The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing. Nucleic Acids Res 2018;46(19):10052–10065. DOI: 10.1093/nar/gky695.
  18. Weng W, Li H, Goel A. Piwi-interacting RNAs (piRNAs) and cancer: emerging biological concepts and potential clinical implications. Biochim Biophys Acta (BBA) – Rev Cancer 2019;1871(1):160–169. DOI: 10.1016/j.bbcan.2018.12.005.
  19. Hombach S, Kretz M. Non-coding RNAs: classification, biology and functioning. Springer International Publishing; 2016. p. 3–17.
  20. Shen J, Zhang W, Qi R, et al. Engineering functional inorganic–organic hybrid systems: advances in siRNA therapeutics. Chem Soc Rev 2018;47(6):1969–1995. DOI: 10.1039/c7cs00479f.
  21. Nikam RR, Gore KR. Journey of siRNA: clinical developments and targeted delivery. Nucleic Acid Ther 2018;28(4):209–224. DOI: 10.1089/nat.2017.0715.
  22. Saw PE, Song EW. siRNA therapeutics: a clinical reality. Sci China Life Sci 2020;63(4):485–500. DOI: 10.1007/s11427-018-9438-y.
  23. Ramakrishnan S. Sno(RNA)wing and pancreatic cancer metastasis. Gastroenterology 2017;153(1):12–14. DOI: 10.1053/j.gastro.2017.05.039.
  24. Bratkovič T, Rogelj B. The many faces of small nucleolar RNAs. Biochim Biophys Acta (BBA) 2014;1839(6):438–443. DOI: 10.1016/j.bbagrm.2014.04.009.
  25. Kristensen LS, Andersen MS, Stagsted LVW, et al. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 2019;20(11):675–691. DOI: 10.1038/s41576-019-0158-7.
  26. Chen I, Chen CY, Chuang TJ. Biogenesis, identification, and function of exonic circular RNAs. Wiley Interdiscip Rev RNA 2015;6(5):563–579. DOI: 10.1002/wrna.1294.
  27. Bolha L, Ravnik-Glavač M, Glavač D. Circular RNAs: biogenesis, function, and a role as possible cancer biomarkers. Int J Genomics 2017;2017:1–19. DOI: 10.1155/2017/6218353.
  28. Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2015;22(3):256–264. DOI: 10.1038/nsmb.2959.
  29. 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):1484–1488. DOI: 10.1126/science.1138341.
  30. Jabandziev P, Bohosova J, Pinkasova T, et al. The emerging role of noncoding RNAs in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2020;26(7):985–993. DOI: 10.1093/ibd/izaa009.
  31. Ulitsky I. Evolution to the rescue: using comparative genomics to understand long non-coding RNAs. Nat Rev Genet 2016;17(10):601–614. DOI: 10.1038/nrg.2016.85.
  32. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell 2013;152(6):1298–1307. DOI: 10.1016/j.cell.2013.02.012.
  33. Yarani R, Mirza AH, Kaur S, et al. The emerging role of lncRNAs in inflammatory bowel disease. Exp Mol Med 2018;50(12):1–14. DOI: 10.1038/s12276-018-0188-9.
  34. Beermann J, Piccoli MT, Viereck J, et al. Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 2016;96(4):1297–1325. DOI: 10.1152/physrev.00041.2015.
  35. 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):143–157. DOI: 10.1038/nrm.2017.104.
  36. 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):409–419. DOI: 10.1016/j.cell.2010.06.040.
  37. Sanders AP, Gennings C, Svensson K, et al. Bacterial cytokine mixtures predict the length of gestation and are associated with miRNA expression in the cervix. Epigenomics 2017;9(1):33–45. DOI: 10.2217/epi-2016-0095.
  38. Elovitz MA, Anton L, Bastek J, et al. Can microRNA profiling in maternal blood identify women at risk for preterm birth? Am J Obstet Gynecol 2015;212(6):782.e1–782.e5. DOI: 10.1016/j.ajog.2015.01.023.
  39. Haneklaus M, Gerlic M, O'Neill LA, et al. miR-223: infection, inflammation and cancer. J Intern Med 2013;274(3):215–226. DOI: 10.1111/joim.12099.
  40. Garg M, Potter JA, Abrahams VM. Identification of microRNAs that regulate TLR2-mediated trophoblast apoptosis and inhibition of IL-6 mRNA. PLoS One 2013;8(10):e77249. DOI: 10.1371/journal.pone.0077249.
  41. Mayor-Lynn K, Toloubeydokhti T, Cruz AC, et al. Expression profile of MicroRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci 2011;18(1):46–56. DOI: 10.1177/1933719110374115.
  42. Renthal NE, Chen CC, Williams KC, et al. miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci 2010;107(48):20828–20833. DOI: 10.1073/pnas.1008301107.
  43. Been JV, Lievense S, Zimmermann LJ, et al. Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis. J Pediatr 2013;162(2):236–242.e2. DOI: 10.1016/j.jpeds.2012.07.012.
  44. Lee J, Kim CJ, Kim JS, et al. Increased miR-223 expression in foetal organs is a signature of acute chorioamnionitis with systemic consequences. J Cell Mol Med 2017;22(2):1179–1189. DOI: 10.1111/jcmm.13377.
  45. Pang Y, Du X, Xu X, et al. Impairment of regulatory T cells in patients with neonatal necrotizing enterocolitis. Int Immunopharmacol 2018;63:19–25. DOI: 10.1016/j.intimp.2018.07.029.
  46. Ma F, Li S, Gao X, et al. Interleukin-6-mediated CCR9(+) interleukin-17-producing regulatory T cells polarization increases the severity of necrotizing enterocolitis. EBioMedicine 2019;44:71–85. DOI: 10.1016/j.ebiom.2019.05.042.
  47. Montenegro D, Romero R, Pineles BL, et al. Differential expression of microRNAs with progression of gestation and inflammation in the human chorioamniotic membranes. Am J Obstet Gynecol 2007;197(3):289.e1–289.e6. DOI: 10.1016/j.ajog.2007.06.027.
  48. Son GH, Kim Y, Lee JJ, et al. MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis. Sci Rep 2019;9(1):19746. DOI: 10.1038/s41598-019-56327-9.
  49. Qian Y, Lu Y, Rui C, et al. Potential significance of circular RNA in human placental tissue for patients with preeclampsia. Cell Physiol Biochem 2016;39(4):1380–1390. DOI: 10.1159/000447842.
  50. Samuels N, van de Graaf RA, de Jonge RCJ, et al. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr 2017;17(1):105. DOI: 10.1186/s12887-017-0847-3.
  51. Boghossian NS, Geraci M, Edwards EM, et al. Morbidity and mortality in small for gestational age infants at 22 to 29 weeks’ gestation. Pediatrics 2018;141(2):e20172533. DOI: 10.1542/peds.2017-2533.
  52. Wang Y, Li SF, Dang YJ, et al. Differentially expressed circular RNAs in maternal and neonatal umbilical cord plasma from SGA compared with AGA. J Cell Biochem 2020;121(1):713–722. DOI: 10.1002/jcb.29317.
  53. MohanKumar K, Namachivayam K, Cheng F, et al. Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis. Pediatr Res 2016;81(1):99–112. DOI: 10.1038/pr.2016.189.
  54. MohanKumar K, Namachivayam K, Song T, et al. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions. Nat Commun 2019;10(1):3494. DOI: 10.1038/s41467-019-11199-5.
  55. De Plaen IG, Liu SX, Tian R, et al. Inhibition of nuclear factor-kappaB ameliorates bowel injury and prolongs survival in a neonatal rat model of necrotizing enterocolitis. Pediatr Res 2007;61(6):716–721. DOI: 10.1203/pdr.0b013e3180534219.
  56. Jilling T, Lu J, Jackson M, et al. Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis. Pediatr Res 2004;55(4):622–629. DOI: 10.1203/01.PDR.0000113463.70435.74.
  57. Jilling T, Simon D, Lu J, et al. The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. J Immunol 2006;177(5):3273–3282. DOI: 10.4049/jimmunol.177.5.3273.
  58. MohanKumar K, Namachivayam K, Chapalamadugu KC, et al. Smad7 interrupts TGF-β signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis. Pediatr Res 2016;79(6):951–961. DOI: 10.1038/pr.2016.18.
  59. Namachivayam K, Blanco CL, MohanKumar K, et al. Smad7 inhibits autocrine expression of TGF-beta2 in intestinal epithelial cells in baboon necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2013;304(2):G167–G180. DOI: 10.1152/ajpgi.00141.2012.
  60. Frank D, Vince JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 2019;26(1):99–114. DOI: 10.1038/s41418-018-0212-6.
  61. Dhuriya YK, Sharma D. Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflammation 2018;15(1):199. DOI: 10.1186/s12974-018-1235-0.
  62. Werts AD, Fulton WB, Ladd MR, et al. A novel role for necroptosis in the pathogenesis of necrotizing enterocolitis. Cell Mol Gastroenterol Hepatol 2020;9(3):403–423. DOI: 10.1016/j.jcmgh.2019.11.002.
  63. Li X, Wang Y, Wang Y, et al. MiR-141-3p ameliorates RIPK1-mediated necroptosis of intestinal epithelial cells in necrotizing enterocolitis. Aging (Albany NY) 2020;12(18):18073–18083. DOI: 10.18632/aging.103608.
  64. Chen H, Zeng L, Zheng W, et al. Increased expression of microRNA-141-3p improves necrotizing enterocolitis of neonates through targeting MNX1. Front Pediatr 2020;8:385. DOI: 10.3389/fped.2020.00385.
  65. Wu YZ, Chan KYY, Leung KT, et al. Dysregulation of miR-431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis. Federation Am Soc Exp Biol J 2019;33(4):5143–5152. DOI: 10.1096/fj.201801470R.
  66. Ng PC, Chan KYY, Yuen TP, et al. Plasma miR-1290 is a novel and specific biomarker for early diagnosis of necrotizing enterocolitis-biomarker discovery with prospective cohort evaluation. J Pediatr 2019;205:83–90.e10. DOI: 10.1016/j.jpeds.2018.09.031.
  67. Imaoka H, Toiyama Y, Fujikawa H, et al. Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. Ann Oncol 2016;27(10):1879–1886. DOI: 10.1093/annonc/mdw279.
  68. van der Sluis M, Vincent A, Bouma J, et al. Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of Muc2 mucin expression in intestinal epithelial cells. Biochem Biophys Res Commun 2008;369(4):1108–1113. DOI: 10.1016/j.bbrc.2008.02.158.
  69. Maheshwari A, Kelly DR, Nicola T, et al. TGF-β2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology 2011;140(1):242–253. DOI: 10.1053/j.gastro.2010.09.043.
  70. Mara MA, Good M, Weitkamp JH. Innate and adaptive immunity in necrotizing enterocolitis. Semin Fetal Neonatal Med 2018;23(6):394–399. DOI: 10.1016/j.siny.2018.08.002.
  71. Yin Y, Qin Z, Xu X, et al. Inhibition of miR-124 improves neonatal necrotizing enterocolitis via an MYPT1 and TLR9 signal regulation mechanism. J Cell Physiol 2019;234(7):10218–10224. DOI: 10.1002/jcp.27691.
  72. Xu Y, Liu Y, Xie H, et al. Profile analysis reveals endogenous RNAs regulate necrotizing enterocolitis progression. Biomed Pharmacother 2020;125:109975. DOI: 10.1016/j.biopha.2020.109975.
  73. Ng WL, Marinov GK, Chin YM, et al. Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway. Sci Rep 2017;7(1):12227. DOI: 10.1038/s41598-017-12550-w.
  74. Ng WL, Marinov GK, Liau ES, et al. Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. RNA Biol 2016;13(9):861–871. DOI: 10.1080/15476286.2016.1207036.
  75. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140(6):805–820. DOI: 10.1016/j.cell.2010.01.022.
  76. Chuang AY, Chuang JC, Zhai Z, et al. NOD2 expression is regulated by microRNAs in colonic epithelial HCT116 cells. Inflamm Bowel Dis 2014;20(1):126–135. DOI: 10.1097/01.MIB.0000436954.70596.9b.
  77. Wu W, He C, Liu C, et al. miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD. Gut 2015;64(11):1755–1764. DOI: 10.1136/gutjnl-2014-307980.
  78. Xu X, Ma C, Liu C, et al. Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis. Biochem Biophys Res Commun 2018;503(2):586–592. DOI: 10.1016/j.bbrc.2018.06.042.
  79. Ghorpade DS, Sinha AY, Holla S, et al. NOD2-nitric oxide-responsive microRNA-146a activates sonic Hedgehog signaling to orchestrate inflammatory responses in murine model of inflammatory bowel disease. J Biol Chem 2013;288(46):33037–33048. DOI: 10.1074/jbc.M113.492496.
  80. Chen Y, Wang C, Liu Y, et al. miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's disease. Biochem Biophys Res Commun 2013;438(1):133–139. DOI: 10.1016/j.bbrc.2013.07.040.
  81. Brain O, Owens BM, Pichulik T, et al. The intracellular sensor NOD2 induces MicroRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity 2013;39(3):521–536. DOI: 10.1016/j.immuni.2013.08.035.
  82. Frakking FN, Brouwer N, Zweers D, et al. High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 2006;145(1):5–12. DOI: 10.1111/j.1365-2249.2006.03093.x.
  83. de Benedetti F, Auriti C, D'Urbano LE, et al. Low serum levels of mannose binding lectin are a risk factor for neonatal sepsis. Pediatr Res 2007;61(3):325–328. DOI: 10.1203/pdr.0b013e318030d12f.
  84. Schlapbach LJ, Latzin P, Regamey N, et al. Mannose-binding lectin cord blood levels and respiratory symptoms during infancy: a prospective birth cohort study. Pediatr Allergy Immunol 2009;20(3):219–226. DOI: 10.1111/j.1399-3038.2008.00782.x.
  85. Takahashi K. Mannose-binding lectin and the balance between immune protection and complication. Expert Rev Anti Infect Ther 2011;9(12):1179–1190. DOI: 10.1586/eri.11.136.
  86. Prencipe G, Azzari C, Moriondo M, et al. Association between mannose-binding lectin gene polymorphisms and necrotizing enterocolitis in preterm infants. J Pediatr Gastroenterol Nutr 2012;55(2):160–165. DOI: 10.1097/MPG.0b013e31824e5f7a.
  87. Xu CY, Dong JF, Chen ZQ, et al. MiR-942-3p promotes the proliferation and invasion of hepatocellular carcinoma cells by targeting MBL2. Cancer Control 2019;26(1):107327481984659. DOI: 10.1177/1073274819846593.
  88. Bowker RM, Yan X, De Plaen IG. Intestinal microcirculation and necrotizing enterocolitis: the vascular endothelial growth factor system. Semin Fetal Neonatal Med 2018;23(6):411–415. DOI: 10.1016/j.siny.2018.08.008.
  89. Crafts TD, Jensen AR, Blocher-Smith EC, et al. Vascular endothelial growth factor: therapeutic possibilities and challenges for the treatment of ischemia. Cytokine 2015;71(2):385–393. DOI: 10.1016/j.cyto.2014.08.005.
  90. Sabnis A, Carrasco R, Liu SX, et al. Intestinal vascular endothelial growth factor is decreased in necrotizing enterocolitis. Neonatology 2015;107(3):191–198. DOI: 10.1159/000368879.
  91. Liu H, Wang YB. Systematic large-scale meta-analysis identifies miRNA-429/200a/b and miRNA-141/200c clusters as biomarkers for necrotizing enterocolitis in newborn. Biosci Rep 2019;39(9):BSR20191503. DOI: 10.1042/BSR20191503.
  92. Zhao J, Yin L, He L. The microRNA landscapes profiling reveals potential signatures of necrotizing enterocolitis in infants. J Comput Biol 2020;27(1):30–39. DOI: 10.1089/cmb.2019.0183.
  93. 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):2005–2015. DOI: 10.1016/j.jacc.2015.07.081.
  94. Fu C, Lv R, Xu G, et al. Circular RNA profile of infantile hemangioma by microarray analysis. PLoS One 2017;12(11):e0187581. DOI: 10.1371/journal.pone.0187581.
  95. Zhou H, Song H, Wu Y, et al. Oxygen-induced circRNA profiles and coregulatory networks in a retinopathy of prematurity mouse model. Exp Ther Med 2019;18(3):2037–2050. DOI: 10.3892/etm.2019.7819.
  96. Guo N, Liu XF, Pant OP, et al. Circular RNAs: novel promising biomarkers in ocular diseases. Int J Med Sci 2019;16(4):513–518. DOI: 10.7150/ijms.29750.
  97. Zhang TR, Huang WQ. Angiogenic circular RNAs: a new landscape in cardiovascular diseases. Microvasc Res 2020;129:103983. DOI: 10.1016/j.mvr.2020.103983.
  98. Ma Z, Shuai Y, Gao X, et al. Circular RNAs in the tumour microenvironment. Mol Cancer 2020;19(1):8. DOI: 10.1186/s12943-019-1113-0.
  99. Giuliani S, Tan YW, Zheng D, et al. Coagulation gene expression profiling in infants with necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 2016;63(6):e169–e175. DOI: 10.1097/MPG.0000000000001215.
  100. Cui YL, Wang B, Gao HM, et al. Interleukin-18 and miR-130a in severe sepsis patients with thrombocytopenia. Patient Prefer Adherence 2016(10):313–319. DOI: 10.2147/PPA.S95588.
  101. Celiker C, Kalkan R. Genetic and epigenetic perspective of microbiota. Appl Microbiol Biotechnol 2020;104(19):8221–8229. DOI: 10.1007/s00253-020-10849-9.
  102. Ray K. IBD. Understanding gut microbiota in new-onset Crohn's disease. Nat Rev Gastroenterol Hepatol 2014;11(5):268. DOI: 10.1038/nrgastro.2014.45.
  103. Ursell LK, Metcalf JL, Parfrey LW, et al. Defining the human microbiome. Nutr Rev 2012;70(Suppl. 1):S38–S44. DOI: 10.1111/j.1753-4887.2012.00493.x.
  104. Goodrich JK, Davenport ER, Beaumont M, et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 2016;19(5):731–743. DOI: 10.1016/j.chom.2016.04.017.
  105. Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell 2014;159(4):789–799. DOI: 10.1016/j.cell.2014.09.053.
  106. Turpin W, Espin-Garcia O, Xu W, et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat Genet 2016;48(11):1413–1417. DOI: 10.1038/ng.3693.
  107. Dempsey J, Zhang A, Cui JY. Coordinate regulation of long non-coding RNAs and protein-coding genes in germ-free mice. BMC Genom 2018;19(1):834. DOI: 10.1186/s12864-018-5235-3.
  108. Liu S, Weiner HL. Control of the gut microbiome by fecal microRNA. Microbial Cell 2016;3(4):176–177. DOI: 10.15698/mic2016.04.492.
  109. Link A, Becker V, Goel A, et al. Feasibility of fecal MicroRNAs as novel biomarkers for pancreatic cancer. PLoS One 2012;7(8):e42933. DOI: 10.1371/journal.pone.0042933.
  110. Ahmed F, Jeffries CD, Vos PW, et al. Diagnostic MicroRNA markers for screening sporadic humancolon cancer and active ulcerative colitis in stool and tissue. Cancer Genom Proteom 2009;6(5):281–295. PMID: 19996134.
  111. Liu S, da Cunha AP, Rezende RM, et al. The host shapes the gut microbiota via fecal MicroRNA. Cell Host Microbe 2016;19(1):32–43. DOI: 10.1016/j.chom.2015.12.005.
  112. Mohan M, Chow CT, Ryan CN, et al. Dietary gluten-induced gut dysbiosis is accompanied by selective upregulation of microRNAs with intestinal tight junction and bacteria-binding motifs in rhesus macaque model of celiac disease. Nutrients 2016;8(11):684. DOI: 10.3390/nu8110684.
  113. Rojas-Feria M, Romero-García T, Fernández Caballero-Rico JÁ, et al. Modulation of faecal metagenome in Crohn's disease: role of microRNAs as biomarkers. World J Gastroenterol 2018;24(46):5223–5233. DOI: 10.3748/wjg.v24.i46.5223.
  114. Ambrozkiewicz F, Karczmarski J, Kulecka M, et al. In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn's disease – a preliminary study. BMC Gastroenterol 2020;20(1):307. DOI: 10.1186/s12876-020-01444-3.
  115. Galley JD, Besner GE. The therapeutic potential of breast milk-derived extracellular vesicles. Nutrients 2020;12(3):745. DOI: 10.3390/nu12030745.
  116. Le Doare K, Holder B, Bassett A, et al. Mother's milk: a purposeful contribution to the development of the infant microbiota and immunity. Front Immunol 2018;9:361. DOI: 10.3389/fimmu.2018.00361.
  117. Carrillo-Lozano E, Sebastián-Valles F, Knott-Torcal C. Circulating microRNAs in breast milk and their potential impact on the infant. Nutrients 2020;12(10):3066. DOI: 10.3390/nu12103066.
  118. Tomé-Carneiro J, Fernández-Alonso N, Tomás-Zapico C, et al. Breast milk microRNAs harsh journey towards potential effects in infant development and maturation. Lipid encapsulation can help. Pharmacol Res 2018;132:21–32. DOI: 10.1016/j.phrs.2018.04.003.
  119. Wu F, Zhi X, Xu R, et al. Exploration of microRNA profiles in human colostrum. Ann Transl Med 2020;8(18):1170–1170. DOI: 10.21037/atm-20-5709.
  120. Liao Y, Du X, Li J, et al. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol Nutr Food Res 2017;61(11):1700082. DOI: 10.1002/mnfr.201700082.
  121. Reif S, Elbaum-Shiff Y, Koroukhov N, et al. Cow and human milk-derived exosomes ameliorate colitis in DSS murine model. Nutrients 2020;12(9):2589. DOI: 10.3390/nu12092589.
  122. Benmoussa A, Diallo I, Salem M, et al. Concentrates of two subsets of extracellular vesicles from cow's milk modulate symptoms and inflammation in experimental colitis. Sci Rep 2019;9(1):14661. DOI: 10.1038/s41598-019-51092-1.
  123. Stremmel W, Weiskirchen R, Melnik BC. Milk exosomes prevent intestinal inflammation in a genetic mouse model of ulcerative colitis: a pilot experiment. Inflamm Intest Dis 2020;5(3):117–123. DOI: 10.1159/000507626.
  124. Pisano C, Galley J, Elbahrawy M, et al. Human breast milk-derived extracellular vesicles in the protection against experimental necrotizing enterocolitis. J Pediatr Surg 2020;55(1):54–58. DOI: 10.1016/j.jpedsurg.2019.09.052.
  125. Li B, Hock A, Wu RY, et al. Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. PLoS One 2019;14(1):e0211431. DOI: 10.1371/journal.pone.0211431.
  126. Karlsson O, Rodosthenous RS, Jara C, et al. Detection of long non-coding RNAs in human breastmilk extracellular vesicles: implications for early child development. Epigenetics 2016;11(10):721–729. DOI: 10.1080/15592294.2016.1216285.
  127. Rubio M, Bustamante M, Hernandez-Ferrer C, et al. Circulating miRNAs, isomiRs and small RNA clusters in human plasma and breast milk. PLoS One 2018;13(3):e0193527. DOI: 10.1371/journal.pone.0193527.
  128. Wang Y, Wei LD, Huan WY, et al. The landscape of circular RNAs and mRNAs in bovine milk exosomes. J Food Compos Analysis 2019;76:33–38. DOI: 10.1016/j.jfca.2018.12.004.
  129. Zeng B, Chen T, Luo J, et al. Exploration of long non-coding RNAs and circular RNAs in porcine milk exosomes. Front Genet 2020;11:652. DOI: 10.3389/fgene.2020.00652.
  130. James JP, Riis LB, Malham M, et al. MicroRNA biomarkers in IBD—differential diagnosis and prediction of colitis-associated cancer. Int J Mol Sci 2020;21(21):7893. DOI: 10.3390/ijms21217893.
  131. Thorlacius-Ussing G, Schnack Nielsen B, Andersen V, et al. Expression and localization of miR-21 and miR-126 in mucosal tissue from patients with inflammatory bowel disease. Inflamm Bowel Dis 2017;23(5):739–752. DOI: 10.1097/MIB.0000000000001086.
  132. Béres NJ, Szabó D, Kocsis D, et al. Role of altered expression of miR-146a, miR-155, and miR-122 in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2016;22(2):327–335. DOI: 10.1097/MIB.0000000000000687.
  133. Valmiki S, Ahuja V, Paul J. MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients. World J Gastroenterol 2017;23(29):5324. DOI: 10.3748/wjg.v23.i29.5324.
  134. Schönauen K, Le N, von Arnim U, et al. Circulating and fecal microRNAs as biomarkers for inflammatory bowel diseases. Inflamm Bowel Dis 2018;24(7):1547–1557. DOI: 10.1093/ibd/izy046.
  135. Feng YH, Tsao CJ. Emerging role of microRNA-21 in cancer. Biomed Rep 2016;5(4):395–402. DOI: 10.3892/br.2016.747.
  136. Hou J, Hu X, Chen B, et al. miR-155 targets Est-1 and induces ulcerative colitis via the IL-23/17/6-mediated Th17 pathway. Pathol Res Practice 2017;213(10):1289–1295. DOI: 10.1016/j.prp.2017.08.001.
  137. Paraskevi A, Theodoropoulos G, Papaconstantinou I, et al. Circulating MicroRNA in inflammatory bowel disease. J Crohns Colitis 2012;6(9):900–904. DOI: 10.1016/j.crohns.2012.02.006.
  138. Shibuya H, Iinuma H, Shimada R, et al. Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology 2010;79(3–4):313–320. DOI: 10.1159/000323283.
  139. Qiao Y, Cai CW, Shen J, et al. Circular RNA expression alterations in colon tissues of Crohn's disease patients. Mol Med Rep 2019;19(5):4500–4506. DOI: 10.3892/mmr.2019.10070.
  140. Wang T, Chen N, Ren W, et al. Integrated analysis of circRNAs and mRNAs expression profile revealed the involvement of hsa_circ_0007919 in the pathogenesis of ulcerative colitis. J Gastroenterol 2019;54(9):804–818. DOI: 10.1007/s00535-019-01585-7.
  141. Yin J, Hu T, Xu L, et al. Circular RNA expression profile in peripheral blood mononuclear cells from Crohn disease patients. Medicine (Baltimore) 2019;98(26):e16072. DOI: 10.1097/MD.0000000000016072.
  142. Xie Y, Zhao Y, Shi L, et al. Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer. J Clin Invest 2020;130(4):2111–2128. DOI: 10.1172/JCI133264.
  143. Slowicka K, Serramito-Gómez I, Boada-Romero E, et al. Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis. Nat Commun 2019;10(1):1834. DOI: 10.1038/s41467-019-09667-z.
  144. Cuna A, George L, Sampath V. Genetic predisposition to necrotizing enterocolitis in premature infants: current knowledge, challenges, and future directions. Semin Fetal Neonatal Med 2018;23(6):387–393. DOI: 10.1016/j.siny.2018.08.006.
  145. Sampath V, Bhandari V, Berger J, et al. A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants. Pediatr Res 2017;81(4):582–588. DOI: 10.1038/pr.2016.260.
  146. Li XX, Xiao L, Chung HK, et al. Interaction between HuR and circPABPN1 modulates autophagy in the intestinal epithelium by altering ATG16L1 translation. Mol Cell Biol 2020;40(6):e00492-19. DOI: 10.1128/MCB.00492-19.
  147. Ye YL, Yin J, Hu T, et al. Increased circulating circular RNA_103516 is a novel biomarker for inflammatory bowel disease in adult patients. World J Gastroenterol 2019;25(41):6273–6288. DOI: 10.3748/wjg.v25.i41.6273.
  148. Lin L, Zhou G, Chen P, et al. Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease? Cell Death Dis 2020;11(6):456. DOI: 10.1038/s41419-020-2657-z.
  149. 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. DOI: 10.1371/journal.pone.0079598.
  150. Liu R, Tang A, Wang X, et al. Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages. Int J Mol Med 2018;42(5):2903–2913. DOI: 10.3892/ijmm.2018.3829.
  151. 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):617–626. DOI: 10.1091/mbc.E15-10-0703.
  152. Mirza AH, Berthelsen CHB, Seemann SE, et al. Transcriptomic landscape of lncRNAs in inflammatory bowel disease. Genome Med 2015;7(1):39. DOI: 10.1186/s13073-015-0162-2.
  153. Qiao Y, Huang ML, Xu AT, et al. LncRNA DQ786243 affects Treg related CREB and Foxp3 expression in Crohn's disease. J Biomed Sci 2013;20(1):87. DOI: 10.1186/1423-0127-20-87.
  154. Quan Y, Song K, Zhang Y, et al. Roseburia intestinalis -derived flagellin is a negative regulator of intestinal inflammation. Biochem Biophys Res Commun 2018;501(3):791–799. DOI: 10.1016/j.bbrc.2018.05.075.
  155. Qiao C, Yang L, Wan J, et al. Long noncoding RNA ANRIL contributes to the development of ulcerative colitis by miR-323b-5p/TLR4/MyD88/NF-кB pathway. Biochem Biophys Res Commun 2019;508(1):217–224. DOI: 10.1016/j.bbrc.2018.11.100.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.