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Journal of Assisted Reproduction and Genetics

Erschienen in:

01.05.2015 | Technological Innovations

MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21

verfasst von: Ji Hyae Lim, Da Eun Lee, Shin Young Kim, Hyun Jin Kim, Kyeong Sun Kim, You Jung Han, Min Hyoung Kim, Jun Seek Choi, Moon Young Kim, Hyun Mee Ryu, So Yeon Park

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2015

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Abstract

Purpose

The objective of this study was to discover a panel of microRNAs (miRNAs) as potential biomarkers for noninvasive prenatal testing (NIPT) of trisomy 21 (T21) and to predict the biological functions of identified biomarkers using bioinformatics tools.

Methods

Using microarray-based genome-wide expression profiling, we compared the expression levels of miRNAs in whole blood samples from non-pregnant women, whole blood samples from pregnant women with euploid or T21 fetuses, and placenta samples from euploid or T21 fetuses. We analyzed the differentially expressed miRNAs according to disease and tissue type (P value <0.05 and two-fold expression change). To predict functions of target genes of miRNAs, the functional annotation tools were used.

Results

We identified 299 miRNAs which reasonably separate the whole blood from the placenta. Among the identified miRNAs, 150 miRNAs were up-regulated in the placenta, and 149 miRNAs were down-regulated. Most of the up-regulated miRNAs in the placenta were members of the mir-498, mir-379, and mir-127 clusters. Among the up-regulated miRNAs in the placenta, mir-1973 and mir-3196 were expressed at higher levels in the T21 placenta than in the euploid placenta. The two miRNAs potentially regulate 203 target genes that are involved in development of brain, central nervous system, and nervous system. The genes are significantly associated with T21-related disorder such as congenital abnormalities, mental disorders, and nervous system diseases.

Conclusions

Our study indicates placenta-specific miRNAs that may be potential biomarkers for NIPT of fetal T21 and provides new insights into the molecular mechanisms of T21 via regulation of miRNAs.

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMed

Du T, Zamore PD. microPrimer: the biogenesis and function of microRNA. Development. 2005;132:4645–52.CrossRefPubMed

Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.CrossRefPubMed

Szulwach KE, Jin P, Alisch RS. Noncoding RNAs in mental retardation. Clin Genet. 2009;75:209–19.CrossRefPubMedCentralPubMed

Huang L, Shen Z, Xu Q, Huang X, Chen Q, Li D. Increased levels of microRNA-424 are associated with the pathogenesis of fetal growth restriction. Placenta. 2013;34:624–7.CrossRefPubMed

Siew WH, Tan KL, Babaei MA, Cheah PS, Ling KH. MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome. Front Cell Neurosci. 2013;7:41.CrossRefPubMedCentralPubMed

Xu Y, Li W, Liu X, Chen H, Tan K, Chen Y, et al. Identification of dysregulated microRNAs in lymphocytes from children with Down syndrome. Gene. 2013;530:278–86.CrossRefPubMed

Xu Y, Li W, Liu X, Ma H, Tu Z, Dai Y. Analysis of microRNA expression profile by small RNA sequencing in Down syndrome fetuses. Int J Mol Med. 2013;32:1115–25.PubMed

Condorelli G, Latronico MV, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol. 2014;63:2177–87.CrossRefPubMed

10.

Kasinski AL, Adams BD, Slack FJ. Aberrant regulation and function of microRNAs in cancer. Curr Biol. 2014;24:R762–76.CrossRefPubMed

11.

Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54:482–90.CrossRefPubMed

12.

Miura K, Miura S, Yamasaki K, Higashijima A, Kinoshita A, Yoshiura K, et al. Identification of pregnancy-associated microRNAs in maternal plasma. Clin Chem. 2010;56:1767–71.CrossRefPubMed

13.

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.CrossRefPubMed

14.

Williams Z, Ben-Dov IZ, Elias R, Mihailovic A, Brown M, Rosenwaks Z, et al. Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations. Proc Natl Acad Sci U S A. 2013;110:4255–60.CrossRefPubMedCentralPubMed

15.

Luo SS, Ishibashi O, Ishikawa G, Ishikawa T, Katayama A, Mishima T, et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod. 2009;81:717–29.CrossRefPubMed

16.

Donker RB, Mouillet JF, Chu T, Hubel CA, Stolz DB, Morelli AE, et al. The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes. Mol Hum Reprod. 2012;18:417–24.CrossRefPubMedCentralPubMed

17.

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedCentralPubMed

18.

Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298–301.CrossRefPubMedCentralPubMed

19.

Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics. 23rd ed. McGraw-Hill’s Medical; 2010. pp. 268.

20.

Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethoré MO, et al. The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med. 2009;11:611–6.CrossRefPubMed

21.

Soifer HS, Rossi JJ, Saetrom P. MicroRNAs in disease and potential therapeutic applications. Mol Ther. 2007;15:2070–9.CrossRefPubMed

22.

Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, et al. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet. 2007;81:405–13.CrossRefPubMedCentralPubMed

23.

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.CrossRefPubMedCentralPubMed

24.

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.PubMedCentralPubMed

25.

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–73.CrossRefPubMed

26.

Babak T, Zhang W, Morris Q, Blencowe BJ, Hughes TR. Probing microRNAs with microarrays: tissue specificity and functional inference. RNA. 2004;10:1813–9.CrossRefPubMedCentralPubMed

27.

Morales-Prieto DM, Ospina-Prieto S, Chaiwangyen W, Schoenleben M, Markert UR. Pregnancy-associated miRNA-clusters. J Reprod Immunol. 2013;97:51–61.CrossRefPubMed

28.

Barch MJ, Knutsen T, Spurbeck JL. The AGT cytogenetics laboratory manual. 3rd ed. New York: Lippincott-Raven; 1997.

29.

R Development Core Team, 2006. R: a language and environment for statistical computing. R Foundation for Statistical Computing (http://www.r-project.org. Access April 10, 2013).

30.

Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34:D140–4.CrossRefPubMedCentralPubMed

31.

Maragkakis M, Reczko M, Simossis VA, Alexiou P, Papadopoulos GL, Dalamagas T, et al. DIANA-microT web server: elucidating microRNA functions through target prediction. Nucleic Acids Res. 2009;37:W273–6.CrossRefPubMedCentralPubMed

32.

Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA.org resource: targets and expression. Nucleic Acids Res. 2008;36:D149–53.CrossRefPubMedCentralPubMed

33.

Wang X. miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA. 2008;14:1012–7.CrossRefPubMedCentralPubMed

34.

Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, et al. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126:1203–17.CrossRefPubMed

35.

Bandyopadhyay S, Mitra R. TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples. Bioinformatics. 2009;25:2625–31.CrossRefPubMed

36.

Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel D. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007;27:91–105.CrossRefPubMedCentralPubMed

37.

Oliveros JC. 2007. VENNY. An interactive tool for comparing lists with Venn Diagrams. Http://bioinfogp.cnb.csic.es/tools/venny/index.html (Access November 20, 2013).

38.

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.CrossRefPubMedCentralPubMed

Titel: MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21
verfasst von: Ji Hyae Lim
Da Eun Lee
Shin Young Kim
Hyun Jin Kim
Kyeong Sun Kim
You Jung Han
Min Hyoung Kim
Jun Seek Choi
Moon Young Kim
Hyun Mee Ryu
So Yeon Park
Publikationsdatum: 01.05.2015
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 5/2015
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-015-0429-y

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MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21