MicroRNA Expression Profile in the Prenatal Amniotic Fluid Samples of Pregnant Women with Down Syndrome

Yıl 2018, Cilt: 35 Sayı: 2, 163 - 166, 01.03.2018

Emin Karaca Ayça Aykut Biray Ertürk Burak Durmaz Ahmet Güler Barış Büke Ahmet Özgür Yeniel Ahmet Mete Ergenoğlu Ferda Özkınay Mehmet Özeren Mert Kazandı Fuat Akercan Sermet Sağol Cumhur Gündüz Özgür Çoğulu

Öz

Background: Down syndrome, which is the most common human chromosomal anomaly that can affect people of any race and age, can be diagnosed prenatally in most cases. Prenatal diagnosis via culture method is time-consuming; thus, genetic analysis has thus been introduced and is continually being developed for rapid prenatal diagnosis. For this reason, the effective use of microRNA profiling for the rapid analysis of prenatal amniotic fluid samples for the diagnosis of Down syndrome was investigated.Aims: To evaluate the expression levels of 14 microRNAs encoded by chromosome 21 in amniotic fluid samples and their utility for prenatal diagnosis of Down syndrome.Study Design: Case-control study.Methods: We performed invasive prenatal testing for 56 pregnant women; 23 carried fetuses with Down syndrome, and 33 carried fetuses with a normal karyotype. Advanced maternal age and increased risk for Down syndrome in the screening tests were indications for invasive prenatal testing. The age of gestation in the study and control groups ranged between 17 and 18 weeks. The expression levels of microRNA were measured by real-time polymerase chain reaction.Results: The expression levels of microRNA-125b-2, microRNA-155, and microRNA-3156 were significantly higher in the study group than in the control group.Conclusion: The presence of significantly dysregulated microRNAs may be associated with either the phenotype or the result of abnormal development. Further large-scale comparative studies conducted in a variety of conditions may bring novel insights in the field of abnormal prenatal conditions.

Anahtar Kelimeler

Down syndrome, microRNAs, amniotic fluid

Kaynakça

• 1. Driscoll DA, Gross S. Clinical practice. Prenatal screening for aneuploidy. N Engl J Med 2009;360:2556-62.
• 2. Ferencz C, Neill CA,Boughman JA, Rubin JD, Brenner JI, Perry LW. Congenital cardiovascular malformations associated with chromosome abnormalities: An epidemiologic study. J Pediatr 1989;114:79-86.
• 3. Cohen WI. Health care guidelines for individuals with Down syndrome: 1999 revision. Down Syndrome Quarterly 1999;4:1-16.
• 4. Elton TS, Sansom SE, Martin MM. Trisomy-21 gene dosage over-expression of miRNAs results in the haploinsufficiency of specific target proteins. RNA Biol 2010;7:540-7.
• 5. Sankaran VG, Menne TF, Scepanovic D, Vergilio JA, Ji P, Kim J, et al. MicroRNA15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci U S A 2011;108:1519-24.
• 6. Ladomery MR, Maddocks DG, Wilson ID. MicroRNAs: their discovery, biogenesis, function and potential use as biomarkers in non-invasive prenatal diagnostics. Int J Mol Epidemiol Genet 2011;2:253-60.
• 7. Go AT, Visser A, van Dijk M, Mulders MA, Eijk P, Ylstra B, et al. A novel method to identify syncytiotrophoblast-derived RNA products representative of trisomy 21 placental RNA in maternal plasma. Methods Mol Biol 2008;444:291-302.
• 8. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS One 2008;3:e3148.
• 9. Gu H, Li H, Zhang L, Luan H, HuangT, Wang L, et al. Diagnostic role of microRNA expression profile in the serum of pregnant women with fetuses with neural tube defects. J Neurochemist 2012;122:641-9.
• 10. Kotlabova K, Doucha J, Hromadnikova I. Placental-specific microRNA in maternal circulation identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol 2011;89:185-91.
• 11. Maccani MA, Padbury JF, Marsit CJ. miR-16 and miR-21 expression in the placenta is associated with fetal growth. PLoS One 2011;6:e21210.
• 12. Enquobahrie DA, Qiu C, Muhie SY, Williams MA. Maternal peripheral blood gene expression in early pregnancy and preeclampsia. Int J Mol Epidemiol Genet 2011;2:78-94.
• 13. Kotlabova K, Doucha J, Chudoba D, Calda P, Dlouha K, Hromadnikova I. Extracellular chromosome 21-derived microRNAs in euploid & aneuploid pregnancies. Indian J Med Res 2013;138:935-43.
• 14. Hromadníková I, Kotlabová K, Doucha J, Chudoba D, Calda P, Dlouhá K. Extracellular chromosome 21-derived microRNAs in maternal circulation: evaluation of their diagnostic potential for screening of Down syndrome. Ceska Gynekol 2012;77:395-402.
• 15. Kamhieh-Milz J, Moftah RF, Bal G, Futschik M, Sterzer V, Khorramshahi O, et al. Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21). Biomed Res Int 2014;2014:402475.
• 16. Kuhn DE, Nuovo GJ, Martin MM, Malana GE, Pleister AP, Jiang J, et al. Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts. Biochem Biophys Res Commun 2008;370:473-7.
• 17. Kuhn DE, Nuovo GJ, Terry AV Jr, Martin MM, Malana GE, Sansom SE, et al. Chromosome 21-derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains. J Biol Chem 2010;285:1529-43.
• 18. Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, et al. Human microRNA-155 on chromosome 21 differentiallyinteractswithitspolymorphictarget in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 2007;81:405-13.
• 19. Szulwach KE, Jin P, Alisch RS. Noncoding RNAs in mental retardation. Clin Genet 2009;75:209-19.
• 20. O'Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008;205:585-94.
• 21. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/ microRNA-155 for normal immune function. Science 2007;316:608-11.
• 22. Fernando TR, Rodriguez-Malave NI, Rao DS. MicroRNAs in B cell development and malignancy. J Hematol Oncol 2012;5:7.
• 23. Zhu S, Cao L, ZhuJ, Kong L, Jin J, Qian L, et al. Identification of maternal serum microRNAs as novel non-invasive biomarkers for prenatal detection of fetal congenital heart defects. Clin Chim Acta 2013;424:66-72.
• 24. Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene 2013;532:1-12.
• 25. Klusmann JH, Li Z, Böhmer K, Maroz A, Koch ML, Emmrich S, et al. miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia. Genes Dev 2010;24:478-90.
• 26. Ozen M, Creighton CJ, Ozdemir M, Ittmann M. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene 2008;27:1788-93.
• 27. Nagayama K, Kohno T, Sato M, Arai Y, Minna JD, Yokota J. Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution. Genes Chromosomes Cancer 2007;46:1000-10.
• 28. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004;101:2999-3004.
• 29. Dong F, Zhang Y, Xia F, Yang Y, Xiong S, Jin L, et al. Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients. Reproduction 2014;148:33-41.
• 30. Xia YF, Pei GH, Wang N, Che YC, Yu FS, Yin FF, et al. miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA. Virol J2017;14:20.