Current Frontiers

MicroRNAs as Epigenetic Targets of Cigarette Smoke During Embryonic Development

Author(s): Ratnam S. Seelan*, Robert M. Greene and Michele M. Pisano

Volume 9 , Issue 3 , 2020

Page: [168 - 173] Pages: 6

DOI: 10.2174/2211536608666190926114704


The adverse developmental effects of exposure to Cigarette Smoke (CS) during pregnancy are documented in this paper. These include low birth weight, congenital anomalies, preterm birth, fetal mortality and morbidity. The current biological thought now recognizes that epigenetics represents a fundamental contributing process in embryogenesis, and that the environment can have a profound effect on shaping the epigenome. It has become increasingly recognized that genes encoding microRNAs (miRNAs) might be potential loci for congenital disabilities. One means by which CS can cause developmental anomalies may be through epigenetic mechanisms involving altered miRNA expression. While several studies have focused on genes affected by CS during embryonic/ fetal development, there is a paucity of knowledge on the involvement of miRNAs in this process. This brief review summarizes the current state of knowledge in this area.

Keywords: Cigarette smoke, e-cigarettes, embryonic development, epigenome, microRNAs, placenta.

Graphical Abstract
U.S. Department of Health and Human Services. Let’s make the next generation tobacco-free: your guide to the 50th anniversary Surgeon General’s report on smoking and health. Atlanta; released 2014; updated 2015.
Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet 2011; 378(9795): 1015-26.
[] [PMID: 21907865]
De Smet EG, Mestdagh P, Vandesompele J, Brusselle GG, Bracke KR. Non-coding RNAs in the pathogenesis of COPD. Thorax 2015; 70(8): 782-91.
[] [PMID: 25995155]
Virdis A, Giannarelli C, Neves MF, Taddei S, Ghiadoni L. Cigarette smoking and hypertension. Curr Pharm Des 2010; 16(23): 2518-25.
[] [PMID: 20550499]
Naqvi AR, Fordham JB, Khan A, Nares S. MicroRNAs responsive to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis LPS modulate expression of genes regulating innate immunity in human macrophages. Innate Immun 2014; 20(5): 540-51.
[] [PMID: 24062196]
Yokoyama Y, Mise N, Suzuki Y, et al. MicroRNAs as potential mediators for cigarette smoking induced atherosclerosis. Int J Mol Sci 2018; 19(4): 1097.
[] [PMID: 29642385]
López-Hernández Y, Rivas-Santiago CE, López JA, Mendoza-Almanza G, Hernandez-Pando R. Tuberculosis and cigarette smoke exposure: An update of in vitro and in vivo studies. Exp Lung Res 2018; 44(2): 113-26.
[] [PMID: 29565741]
Holbrook BD. The effects of nicotine on human fetal development. Birth Defects Res C Embryo Today 2016; 108(2): 181-92.
[] [PMID: 27297020]
Mund M, Louwen F, Klingelhoefer D, Gerber A. Smoking and pregnancy--a review on the first major environmental risk factor of the unborn. Int J Environ Res Public Health 2013; 10(12): 6485-99.
[] [PMID: 24351784]
U.S. Department of Health and Human Services. The health consequences of smoking-50 years of progress. A report of the surgeon general. Atlanta, GA. Centers for disease control and prevention, National Center for chronic disease prevention and health promotion, office on smoking and health. 2014.
Kurti AN, Redner R, Lopez AA, et al. Tobacco and nicotine delivery product use in a national sample of pregnant women. Prev Med 2017; 104: 50-6.
[] [PMID: 28789981]
Wyszynski DF, Duffy DL, Beaty TH. Maternal cigarette smoking and oral clefts: a meta-analysis. Cleft Palate Craniofac J 1997; 34(3): 206-10.
[] [PMID: 9167070]
Little J, Cardy A, Munger RG. Tobacco smoking and oral clefts: a meta-analysis. Bull World Health Organ 2004; 82(3): 213-8.
[PMID: 15112010]
Ozturk F, Sheldon E, Sharma J, Canturk KM, Otu HH, Nawshad A. Nicotine exposure during pregnancy results in persistent midline epithelial seam with improper palatal fusion. Nicotine Tob Res 2016; 18(5): 604-12.
[] [PMID: 26443016]
Chen G, Li MX, Wang HX, et al. Identification of key genes in cleft lip with or without cleft palate regulated by miR-199a-5p. Int J Pediatr Otorhinolaryngol 2018; 111: 128-37.
[] [PMID: 29958595]
Wu N, Yan J, Han T, Zou J, Shen W. Integrated assessment of differentially expressed plasma microRNAs in subtypes of nonsyndromic orofacial clefts. Medicine (Baltimore) 2018; 97(25): e11224
[] [PMID: 29924053]
Grassia V, Lombardi A, Kawasaki H, et al. Salivary microRNAs as new molecular markers in cleft lip and palate: a new frontier in molecular medicine. Oncotarget 2018; 9(27): 18929-38.
[] [PMID: 29721173]
Kumari P, Singh SK, Raman R. A novel non-coding RNA within an intron of CDH2 and association of its SNP with non-syndromic cleft lip and palate. Gene 2018; 658: 123-8.
[] [PMID: 29524576]
Margolis KA, Bernat JK, Keely O’Brien E, Delahanty JC. Online information about harmful tobacco constituents: a content analysis. Nicotine Tob Res 2017; 19(10): 1209-15.
[PMID: 27613931]
Russ R, Slack FJ. Cigarette-smoke-induced dysregulation of microRNA expression and its role in lung carcinogenesis. Pulm Med 2012; 2012: 791234
[] [PMID: 22191027]
Izzotti A, Calin GA, Steele VE, Croce CM, De Flora S. Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light. FASEB J 2009; 23(9): 3243-50.
[] [PMID: 19465468]
Izzotti A, Calin GA, Arrigo P, Steele VE, Croce CM, De Flora S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J 2009; 23(3): 806-12.
[] [PMID: 18952709]
England LJ, Aagaard K, Bloch M, et al. Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products. Neurosci Biobehav Rev 2017; 72: 176-89.
[] [PMID: 27890689]
Pearson JL, Richardson A, Niaura RS, Vallone DM, Abrams DB. e-Cigarette awareness, use, and harm perceptions in US adults. Am J Public Health 2012; 102(9): 1758-66.
[] [PMID: 22813087]
Bhandari NR, Day KD, Payakachat N, Franks AM, McCain KR, Ragland D. Use and risk perception of electronic nicotine delivery systems and tobacco in pregnancy. Womens Health Issues 2018; 28(3): 251-7.
[] [PMID: 29588116]
Mark KS, Farquhar B, Chisolm MS, Coleman-Cowger VH, Terplan M. Knowledge, attitudes, and practice of electronic cigarette use among pregnant women. J Addict Med 2015; 9(4): 266-72.
[] [PMID: 25974378]
Wagner NJ, Camerota M, Propper C. Prevalence and perceptions of electronic cigarette use during pregnancy. Matern Child Health J 2017; 21(8): 1655-61.
[] [PMID: 28084577]
Greene RM, Pisano MM. Developmental toxicity of e-cigarette aerosols. Birth Defects Res 2019; 111(17): 1294-301.
[] [PMID: 31400084]
Kennedy AE, Kandalam S, Olivares-Navarrete R, Dickinson AJG. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells. PLoS One 2017; 12(9): e0185729
[] [PMID: 28957438]
Lee MS, Allen JG, Christiani DC. Endotoxin and (1→3)-β-D-Glucan contamination in electronic cigarette products sold in the United States. Environ Health Perspect 2019; 127(4): 47008.
[] [PMID: 31017484]
Omaiye EE, McWhirter KJ, Luo W, Pankow JF, Talbot P. High nicotine electronic cigarette products: toxicity of JUUL fluids and aerosols correlates strongly with nicotine and some flavor chemical concentrations. Chem Res Toxicol 2019; 32(6): 1058-69.
[] [PMID: 30896936]
Singh SK, Pal Bhadra M, Girschick HJ, Bhadra U. MicroRNAs--micro in size but macro in function. FEBS J 2008; 275(20): 4929-44.
[] [PMID: 18754771]
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[] [PMID: 19167326]
Karp X, Ambros V. Developmental biology. Encountering microRNAs in cell fate signaling. Science 2005; 310(5752): 1288-9.
[] [PMID: 16311325]
Xu P, Guo M, Hay BA. MicroRNAs and the regulation of cell death. Trends Genet 2004; 20(12): 617-24.
[] [PMID: 15522457]
Kato M, Slack FJ. microRNAs: small molecules with big roles - C. elegans to human cancer. Biol Cell 2008; 100(2): 71-81.
[] [PMID: 18199046]
Kulshreshtha R, Ferracin M, Wojcik SE, et al. A microRNA signature of hypoxia. Mol Cell Biol 2007; 27(5): 1859-67.
[] [PMID: 17194750]
Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 2005; 33(4): 1290-7.
[] [PMID: 15741182]
Afonso-Grunz F, Müller S. Principles of miRNA-mRNA interactions: beyond sequence complementarity. Cell Mol Life Sci 2015; 72(16): 3127-41.
[] [PMID: 26037721]
Dragomir MP, Knutsen E, Calin GA. SnapShot: Unconventional miRNA Functions. Cell 2018; 174(4): 1038-1038.e1.
[] [PMID: 30096304]
Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101(9): 2999-3004.
[] [PMID: 14973191]
Ligorio M, Izzotti A, Pulliero A, Arrigo P. Mutagens interfere with microRNA maturation by inhibiting DICER. An in silico biology analysis. Mutat Res 2011; 717(1-2): 116-28.
[] [PMID: 21889945]
Gross TJ, Powers LS, Boudreau RL, et al. A microRNA processing defect in smokers’ macrophages is linked to SUMOylation of the endonuclease DICER. J Biol Chem 2014; 289(18): 12823-34.
[] [PMID: 24668803]
Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med 2009; 180(5): 462-7.
[] [PMID: 19498054]
Maccani MA, Knopik VS. Cigarette smoke exposure-associated alterations to non-coding RNA. Front Genet 2012; 3: 53.
[] [PMID: 22509180]
Mullany LE, Herrick JS, Wolff RK, Stevens JR, Slattery ML. Association of cigarette smoking and microRNA expression in rectal cancer: Insight into tumor phenotype. Cancer Epidemiol 2016; 45: 98-107.
[] [PMID: 27780077]
Shen W, Liu J, Zhao G, et al. Repression of Toll-like receptor-4 by microRNA-149-3p is associated with smoking-related COPD. Int J Chron Obstruct Pulmon Dis 2017; 12: 705-15.
[] [PMID: 28260877]
Advani J, Subbannayya Y, Patel K, et al. Long-term cigarette smoke exposure and changes in miRNA expression and proteome in non-small-cell lung cancer. OMICS 2017; 21(7): 390-403.
[] [PMID: 28692419]
Krishnan AR, Zheng H, Kwok JG, et al. A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma. Oral Oncol 2017; 72: 56-64.
[] [PMID: 28797462]
Izzotti A, Balansky R, Ganchev G, et al. Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice. Oncotarget 2016; 7(51): 84758-74.
[] [PMID: 27713172]
Takahashi K, Yokota S, Tatsumi N, Fukami T, Yokoi T, Nakajima M. Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects. Toxicol Appl Pharmacol 2013; 272(1): 154-60.
[] [PMID: 23726802]
Xi S, Inchauste S, Guo H, et al. Cigarette smoke mediates epigenetic repression of miR-217 during esophageal adenocarcinogenesis. Oncogene 2015; 34(44): 5548-59.
[] [PMID: 25703328]
Xi S, Xu H, Shan J, et al. Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis. J Clin Invest 2013; 123(3): 1241-61.
[] [PMID: 23426183]
Fröhlich E. [Structure and function of blood-tissue barriers]. Dtsch Med Wochenschr 2002; 127(49): 2629-34.
[PMID: 12469278]
Maccani MA, Avissar-Whiting M, Banister CE, McGonnigal B, Padbury JF, Marsit CJ. Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21, and miR-146a in the placenta. Epigenetics 2010; 5(7): 583-9.
[] [PMID: 20647767]
Knopik VS, Maccani MA, Francazio S, McGeary JE. The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Dev Psychopathol 2012; 24(4): 1377-90.
[] [PMID: 23062304]
Herberth G, Bauer M, Gasch M, et al. Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk study group. Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers. J Allergy Clin Immunol 2014; 133(2): 543-50.
[] [PMID: 23978443]
Eberhart JK, He X, Swartz ME, et al. MicroRNA miRN140 modulates PDGF signaling during palatogenesis. Nat Genet 2008; 40(3): 290-8.
[] [PMID: 18264099]
Li L, Zhu GQ, Meng T, et al. Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate. Am J Med Genet A 2011; 155A(12): 2940-8.
[] [PMID: 22012839]
Xu X, Bringas P Jr, Soriano P, Chai Y. PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis. Dev Dyn 2005; 232(1): 75-84.
[] [PMID: 15543606]
Zhang Y, Pan T, Zhong X, Cheng C. Nicotine upregulates microRNA-21 and promotes TGF-β-dependent epithelial-mesenchymal transition of esophageal cancer cells. Tumour Biol 2014; 35(7): 7063-72.
[] [PMID: 24756761]
Maestri NE, Beaty TH, Hetmanski J, et al. Application of transmission disequilibrium tests to nonsyndromic oral clefts: including candidate genes and environmental exposures in the models. Am J Med Genet 1997; 73(3): 337-44.
[<337:AID-AJMG21>3.0.CO;2-J] [PMID: 9415696]
Marczylo EL, Amoako AA, Konje JC, Gant TW, Marczylo TH. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics 2012; 7(5): 432-9.
[] [PMID: 22441141]
Furlong HC, Stämpfli MR, Gannon AM, Foster WG. Identification of microRNAs as potential markers of ovarian toxicity. J Appl Toxicol 2018; 38(5): 744-52.
[] [PMID: 29377183]
Vrijens K, Bollati V, Nawrot TS. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect 2015; 123(5): 399-411.
[] [PMID: 25616258]
Li J, Wu Z, Cheng F, Li W, Liu G, Tang Y. Computational prediction of microRNA networks incorporating environmental toxicity and disease etiology. Sci Rep 2014; 4: 5576.
[] [PMID: 24992957]
Luck W, Nau H, Hansen R, Steldinger R. Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers. Dev Pharmacol Ther 1985; 8(6): 384-95.
[] [PMID: 4075937]

© 2022 Bentham Science Publishers | Privacy Policy