Advertisement

Environmental Science and Pollution Research

, Volume 26, Issue 33, pp 34421–34429 | Cite as

Differentially expressed circular RNAs in air pollution–exposed rat embryos

  • Zheng Li
  • Jianqing Ma
  • Jianxiong ShenEmail author
  • Matthew T. V. Chan
  • William K. K. Wu
  • Zhanyong WuEmail author
Research Article

Abstract

Circular RNAs (circRNAs) are an important class of non-coding RNAs partly by acting as microRNA sponges. Growing evidence indicates that air pollution exposure during pregnancy could lead to congenital defects in the offspring. In this study, using circRNAs sequencing, we profiled differentially expressed circRNAs in rat embryos exposed to a high concentration (> 200 μg/m3) of fine particulate matter (PM2.5) in utero. Compared with the control embryos whose mothers were reared in clean air, 25 and 55 circRNAs were found to be downregulated and upregulated, respectively, in the air pollution–exposed group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of circRNA-coexpressed genes indicated that segmentation, brain development, and system development together with lysine degradation, Rap1 signaling pathway, and adrenergic signaling were deregulated by in utero air pollution exposure. We also identified the central role of three circRNAs, namely circ_015003, circ_030724, and circ_127215 in the circRNA-microRNA interaction network. These data suggested that circRNA deregulation might play a crucial role in the development of air pollution–associated congenital malformations.

Keywords

circRNAs Circular RNAs Air pollution Congenital spinal malformations 

Notes

Compliance with ethical standards

This animal study was approved by the Ethics Committee of the author’s institution and was carried out in accordance with our previous study.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Arnaiz E, Sole C, Manterola L, Iparraguirre L, Otaegui D, Lawrie CH (2019) CircRNAs and cancer: biomarkers and master regulators. Semin Cancer Biol 58:90–99Google Scholar
  2. Aulehla A, Pourquié O (2008) Oscillating signaling pathways during embryonic development. Curr Opin Cell Biol 20:632–637Google Scholar
  3. Blay V, Barrios Rivas JL, Xiao Z (2019) Separation of air components and pollutants by the Earth’s gravitational field. Chemosphere 232:453–461Google Scholar
  4. Chen LL (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17:205–211Google Scholar
  5. Chen X, Chen RX, Wei WS, Li YH, Feng ZH, Tan L, Chen JW, Yuan GJ, Chen SL, Guo SJ, Xiao KH, Liu ZW, Luo JH, Zhou FJ, Xie D (2018) PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res 24:6319–6330Google Scholar
  6. Cheng WJ, Liang SJ, Huang CS, Lin CL, Pien LC, Hang LW (2019) Air pollutants are associated with obstructive sleep apnea severity in non-rapid eye movement sleep. J Clin Sleep Med 15(6):831–837Google Scholar
  7. Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160:1125–1134Google Scholar
  8. Cui X, Li F, Xiang J, Fang L, Chung MK, Day DB, Mo J, Weschler CJ, Gong J, He L, Zhu D, Lu C, Han H, Zhang Y, Zhang JJ (2018) Cardiopulmonary effects of overnight indoor air filtration in healthy non-smoking adults: a double-blind randomized crossover study. Environ Int 114:27–36Google Scholar
  9. Han B, Chao J, Yao H (2018) Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther 187:31–44Google Scholar
  10. He T, Zhu J, Wang J, Ren X, Cheng G, Liu X, Ma Q, Zhang Y, Li Z, Ba Y (2018) Ambient air pollution, H19/DMR methylation in cord blood and newborn size: a pilot study in Zhengzhou City, China. Chemosphere 212:863–871Google Scholar
  11. He X, Chen Y, Zhang C, Gong W, Zhang X, Nie S (2018c) Polycyclic aromatic hydrocarbons from particulate matter 2.5 (PM2.5) in polluted air changes miRNA profile related to cardiovascular disease. Med Sci Monit 24:5925–5934Google Scholar
  12. Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, Kohlmaier A, Herbst A, Northoff BH, Nicolaou A, Gäbel G, Beutner F, Scholz M, Thiery J, Musunuru K, Krohn K, Mann M, Teupser D (2016) Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun 7:12429Google Scholar
  13. Jacobs-McDaniels NL, Albertson RC (2011) Chd7 plays a critical role in controlling left-right symmetry during zebrafish somitogenesis. Dev Dyn 240:2272–2280Google Scholar
  14. Li Z, Shen J, Wu WK, Wang X, Liang J, Qiu G, Liu J (2012) Vitamin A deficiency induces congenital spinal deformities in rats. PLoS One 7:e46565Google Scholar
  15. Li X, Yang L, Chen LL (2018) The biogenesis, functions, and challenges of circular RNAs. Mol Cell 71:428–442Google Scholar
  16. Li Z, Ma J, Bi J, Guo H, Chan MTV, Wu WKK, Wu Z, Shen J (2019) MicroRNA signature of air pollution exposure-induced congenital defects. J Cell Physiol 234(10):17896–17904Google Scholar
  17. Lim CC, Hayes RB, Ahn J, Shao Y, Silverman DT, Jones RR, Thurston GD (2019) Mediterranean diet and the association between air pollution and cardiovascular disease mortality risk. Circulation 139:1766–1775Google Scholar
  18. Lin H, Zhang X, Feng N, Wang R, Zhang W, Deng X, Wang Y, Yu X, Ye X, Li L, Qian Y, Yu H, Qian B (2018) LncRNA LCPAT1 mediates smoking/ particulate matter 2.5-induced cell autophagy and epithelial-mesenchymal transition in lung cancer cells via RCC2. Cell Physiol Biochem 47:1244–1258Google Scholar
  19. Liu H, Hu Y, Zhuang B, Yin J, Chen X-H, Wang J, Li M-M, Xu J, Wang X-Y, Yu Z-B, Han S-P (2018) Differential expression of circRNAs in embryonic heart tissue associated with ventricular septal defect. Int J Med Sci 15:703–712Google Scholar
  20. Liu CX, Li X, Nan F, Jiang S, Gao X, Guo SK, Xue W, Cui Y, Dong K, Ding H, Qu B, Zhou Z, Shen N, Yang L, Chen LL (2019) Structure and degradation of circular RNAs regulate PKR activation in innate immunity. Cell 177:865–880.e21Google Scholar
  21. Liu Y, Pan J, Zhang H, Shi C, Li G, Peng Z, Ma J, Zhou Y, Zhang L (2019a) Short-term exposure to ambient air pollution and asthma mortality. Am J Respir Crit Care Med 200(1):24–32Google Scholar
  22. Liu Z, Ran Y, Tao C, Li S, Chen J, Yang E (2019b) Detection of circular RNA expression and related quantitative trait loci in the human dorsolateral prefrontal cortex. Genome Biol 20:99Google Scholar
  23. Maass PG, Glažar P, Memczak S, Dittmar G, Hollfinger I, Schreyer L, Sauer AV, Toka O, Aiuti A, Luft FC, Rajewsky N (2017) A map of human circular RNAs in clinically relevant tissues. J Mol Med (Berl) 95:1179–1189Google Scholar
  24. Mariet AS, Mauny F, Pujol S, Thiriez G, Sagot P, Riethmuller D, Boilleaut M, Defrance J, Houot H, Parmentier AL, Vasseur-Barba M, Benzenine E, Quantin C, Bernard N (2018) Multiple pregnancies and air pollution in moderately polluted cities: is there an association between air pollution and fetal growth? Environ Int 121:890–897Google Scholar
  25. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338Google Scholar
  26. Morelli X, Gabet S, Rieux C, Bouscasse H, Mathy S, Slama R (2019) Which decreases in air pollution should be targeted to bring health and economic benefits and improve environmental justice? Environ Int 129:538–550Google Scholar
  27. Newbury JB, Arseneault L, Beevers S, Kitwiroon N, Roberts S, Pariante CM, Kelly FJ, Fisher HL (2019) Association of air pollution exposure with psychotic experiences during adolescence. JAMA Psychiatry 76(6):614–623Google Scholar
  28. Okubo Y, Sugawara T, Abe-Koduka N, Kanno J, Kimura A, Saga Y (2012) Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling. Nat Commun 3:1141Google Scholar
  29. Pickett EA, Olsen GS, Tallquist MD (2008) Disruption of PDGFRalpha-initiated PI3K activation and migration of somite derivatives leads to spina bifida. Development 135:589–598Google Scholar
  30. Schneider T, Bindereif A (2017) Circular RNAs: coding or noncoding? Cell Res 27:724–725Google Scholar
  31. Schraufnagel DE, Balmes JR, Cowl CT, De Matteis S, Jung SH, Mortimer K, Perez-Padilla R, Rice MB, Riojas-Rodriguez H, Sood A, Thurston GD, To T, Vanker A, Wuebbles DJ (2019) Air pollution and noncommunicable diseases: a review by the forum of international respiratory societies’ environmental committee, Part 2: air pollution and organ systems. Chest 155:417–426Google Scholar
  32. Schulte C, Barwari T, Joshi A, Theofilatos K, Zampetaki A, Barallobre-Barreiro J, Singh B, Sörensen NA, Neumann JT, Zeller T, Westermann D, Blankenberg S, Marber M, Liebetrau C, Mayr M (2019) Comparative analysis of circulating non-coding RNAs versus protein biomarkers in the detection of myocardial injury. Circ Res 125(3):328–340Google Scholar
  33. Shen S, Wu Y, Chen J, Xie Z, Huang K, Wang G, Yang Y, Ni W, Chen Z, Shi P, Ma Y, Fan S (2019) CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene. Ann Rheum Dis 78:826–836Google Scholar
  34. Shin SW, Bae DJ, Park CS, Lee JU, Kim RH, Kim SR, Chang HS, Park JS (2019) Effects of air pollution on moderate and severe asthma exacerbations. J Asthma.  https://doi.org/10.1080/02770903.2019.1611844
  35. Smit-McBride Z, Nguyen J, Elliott GW, Wang Z, McBride RA, Nguyen AT, Oltjen SL, Yiu G, Thomasy SM, Pinkerton KE, Lee ES, Cunefare D, Farsiu S, Morse LS (2018) Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque. Mol Vis 24:633–646Google Scholar
  36. Sofianopoulou E et al (2019) Traffic exposures, air pollution and outcomes in pulmonary arterial hypertension: a UK cohort study analysis. Eur Respir J 53(5).  https://doi.org/10.1183/13993003.01429-2018 Google Scholar
  37. Sram RJ, Binkova B, Dostal M, Merkerova-Dostalova M, Libalova H, Milcova A, Rossner P Jr, Rossnerova A, Schmuczerova J, Svecova V, Topinka J, Votavova H (2013) Health impact of air pollution to children. Int J Hyg Environ Health 216:533–540Google Scholar
  38. Sweetman D, Rathjen T, Jefferson M, Wheeler G, Smith TG, Wheeler GN, Munsterberg A, Dalmay T (2006) FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos. Dev Dyn 235:2185–2191Google Scholar
  39. Szabo L, Salzman J (2016) Detecting circular RNAs: bioinformatic and experimental challenges. Nat Rev Genet 17:679–692Google Scholar
  40. Tsai SS, Chiu HF, Yang CY (2019) Ambient air pollution and hospital admissions for peptic ulcers in Taipei: a time-stratified case-crossover study. Int J Environ Res Public Health 16(11).  https://doi.org/10.3390/ijerph16111916 Google Scholar
  41. Tsamou M, Vrijens K, Madhloum N, Lefebvre W, Vanpoucke C, Nawrot TS (2018) Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach. Epigenetics 13:135–146Google Scholar
  42. Usemann J, Decrue F, Korten I, Proietti E, Gorlanova O, Vienneau D, Fuchs O, Latzin P, Röösli M, Frey U, BILD study group (2019) Exposure to moderate air pollution and associations with lung function at school-age: a birth cohort study. Environ Int 126:682–689Google Scholar
  43. Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P (2005) Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science 308:563–566Google Scholar
  44. Vilhais-Neto GC, Maruhashi M, Smith KT, Vasseur-Cognet M, Peterson AS, Workman JL, Pourquie O (2010) Rere controls retinoic acid signalling and somite bilateral symmetry. Nature 463:953–957Google Scholar
  45. Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, Wu YM, Dhanasekaran SM, Engelke CG, Cao X, Robinson DR, Nesvizhskii AI, Chinnaiyan AM (2019) The landscape of circular RNA in cancer. Cell 176:869–881.e13Google Scholar
  46. Wang C, Bi J, Olde Rikkert MGM (2018) Early warning signals for critical transitions in cardiopulmonary health, related to air pollution in an urban Chinese population. Environ Int 121:240–249Google Scholar
  47. Wesselhoeft RA, Kowalski PS, Anderson DG (2018) Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat Commun 9:2629Google Scholar
  48. Wooding DJ, Ryu MH, Hüls A, Lee AD, Lin DTS, Rider CF, Yuen ACY, Carlsten C (2019) Particle depletion does not remediate acute effects of traffic-related air pollution and allergen: a randomized, double-blinded crossover study. Am J Respir Crit Care Med 200(5):565–574Google Scholar
  49. Xing J, Zhang F, Zhou Y, Wang S, Ding D, Jang C, Zhu Y, Hao J (2019) Least-cost control strategy optimization for air quality attainment of Beijing-Tianjin-Hebei region in China. J Environ Manag 245:95–104Google Scholar
  50. Zhang Z, O’Rourke JR, McManus MT, Lewandoski M, Harfe BD, Sun X (2011) The microRNA-processing enzyme Dicer is dispensable for somite segmentation but essential for limb bud positioning. Dev Biol 351:254–265Google Scholar
  51. Zhang M, Zhao K, Xu X, Yang Y, Yan S, Wei P, Liu H, Xu J, Xiao F, Zhou H, Yang X, Huang N, Liu J, He K, Xie K, Zhang G, Huang S, Zhang N (2018) A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat Commun 9:4475Google Scholar
  52. Zhang Y, Wang J, Chen L, Yang H, Zhang B, Wang Q, Hu L, Zhang N, Vedal S, Xue F, Bai Z (2019) Ambient PM and clinically recognized early pregnancy loss: a case-control study with spatiotemporal exposure predictions. Environ Int 126:422–429Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.Department of Orthopedic SurgeryThe General Hospital of Xingtai Mining Industry Bloc., Orthopaedic Hospital of XingtaiXingtaiChina
  3. 3.Department of Anaesthesia and Intensive CareThe Chinese University of Hong KongHong KongChina
  4. 4.State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina

Personalised recommendations