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Article Open Access

Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome

  • Authors:
    • Miao Chai
    • Liju Su
    • Xiaolei Hao
    • Meng Zhang
    • Lihui Zheng
    • Jiabing Bi
    • Xiao Han
    • Chunbo Gao
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The First Hospital of Harbin, Harbin, Heilongjiang 150010, P.R. China
  • Pages: 2063-2072
    |
    Published online on: June 27, 2019
       https://doi.org/10.3892/mmr.2019.10433
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Abstract

The present bioinformatics analysis was performed using a multi‑step approach to identify a microRNA (miR)‑mRNA regulatory network in Down syndrome. miR (GSE69210) and mRNA (GSE70573) data was downloaded and collected from the thymic tissues of both Down syndrome and karyotypically normal subjects and placed in a public repository. Then, weighted gene co‑expression network analysis (WGCNA) was performed to screen for miRs and mRNAs associated with Down syndrome. Subsequently, differentially expressed miRs (DEmiRs) and mRNAs/differentially expressed genes (DEGs) were identified following screening and mapping to RNA data. Bidirectional hierarchical clustering analysis was then performed to distinguish DEmiRs and DEGs between Down syndrome samples and normal control samples. DEmiR targets were retrieved using the miRanda database and mapped to the mRNA module screen by WGCNA. A gene co‑expression network was constructed and subjected to functional enrichment analysis. During WGCNA, a total of 6 miR modules and 20 mRNA modules associated with Down syndrome were identified. Following mapping of these miRs and mRNAs to the miR and mRNA modules screened using WGNCA, a total of 12 DEmiRs and 237 DEGs were collected. Following comparison with DEmiR targets retrieved from the miRanda database, a total of 255 DEmiR‑DEG pairs, including 6 DEmiRs and 106 DEGs were obtained. At expression correlation coefficient >0.9, a total of 231 gene pairs were selected. These gene pairs were enriched in response to stress and response to stimuli following functional annotation and module division. An integrated analysis of miR and mRNA expression in the thymus in Down syndrome is reported in the present study. miR‑30c, miR‑145, miR‑183 and their targets may serve important roles in the pathogenesis and development of complications in Down syndrome. However, further experimental studies are required to verify these results.
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1 

Weijerman ME and de Winter JP: Clinical practice: The care of children with Down syndrome. Eur J Pediatr. 169:1445–1452. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Patterson D: Molecular genetic analysis of Down syndrome. Hum Genet. 126:195–214. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Gardiner KJ: Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci. 31:66–73. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Hickey F, Hickey E and Summar KL: Medical update for children with Down syndrome for the pediatrician and family practitioner. Adv Pediatr. 59:137–157. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Jin S, Lee YK, Lim YC, Zheng Z, Lin XM, Ng DP, Holbrook JD, Law HY, Kwek KY, Yeo GS and Ding C: Global DNA hypermethylation in down syndrome placenta. PLoS Genet. 9:e10035152013. View Article : Google Scholar : PubMed/NCBI

6 

Costa V, Angelini C, D'Apice L, Mutarelli M, Casamassimi A, Sommese L, Gallo MA, Aprile M, Esposito R, Leone L, et al: Massive-scale RNA-Seq analysis of non ribosomal transcriptome in human trisomy 21. PLoS One. 6:e184932011. View Article : Google Scholar : PubMed/NCBI

7 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Liao JM, Zhou X, Zhang Y and Lu H: MiR-1246: A new link of the p53 family with cancer and Down syndrome. Cell Cycle. 11:2624–2630. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Shi WL, Liu ZZ, Wang HD, Wu D, Zhang H, Xiao H, Chu Y, Hou QF and Liao SX: Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome. J Biomed Sci. 23:482016. View Article : Google Scholar : PubMed/NCBI

11 

Letourneau A, Santoni FA, Bonilla X, Sailani MR, Gonzalez D, Kind J, Chevalier C, Thurman R, Sandstrom RS, Hibaoui Y, et al: Domains of genome-wide gene expression dysregulation in Down's syndrome. Nature. 508:345–350. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Levin S, Schlesinger M, Handzel Z, Hahn T, Altman Y, Czernobilsky B and Boss J: Thymic deficiency in Down's syndrome. Pediatrics. 63:80–87. 1979.PubMed/NCBI

13 

Larocca LM, Lauriola L, Ranelletti FO, Piantelli M, Maggiano N, Ricci R and Capelli A: Morphological and immunohistochemical study of Down syndrome thymus. Am J Med Genet. (Suppl 37):225–230. 1990.

14 

Moreira-Filho CA, Bando SY, Bertonha FB, Silva FN, Costa Lda F, Ferreira LR, Furlanetto G, Chacur P, Zerbini MC and Carneiro-Sampaio M: Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants. Oncotarget. 7:7497–7533. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Smyth GK: LIMMA: Linear models for microarray data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Gentleman R, Carey V, Dudoit S, Irizarry R and Huber W: Springer; New York, NY: pp. 397–420. 2005, View Article : Google Scholar

16 

R Core Team: R, . A Language and environment for statistical computing. Version 3.3.3. R Foundation for Statistical Computing; Vienna: 2017

17 

Smyth G: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 3:Article32004. View Article : Google Scholar : PubMed/NCBI

18 

Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z, Zhu G, Qi J, Ma H, Nian H and Wang Y: RNA-seq analyses of multiple meristems of soybean: Novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biol. 14:1692014. View Article : Google Scholar : PubMed/NCBI

19 

Betel D, Koppal A, Agius P, Sander C and Leslie C: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol. 11:R902010. View Article : Google Scholar : PubMed/NCBI

20 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Ehsani Ardakani MJ, Safaei A, Arefi Oskouie A, Haghparast H, Haghazali M, Mohaghegh Shalmani H, Peyvandi H, Naderi N and Zali MR: Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks. Gastroenterol Hepatol Bed Bench. 9 (Suppl 1):S14–S22. 2016.PubMed/NCBI

22 

Maere S, Heymans K and Kuiper M: BiNGO: A Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 21:3448–3449. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Beissbarth T and Speed TP: GOstat: Find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics. 20:1464–1465. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Wu J, Mao X, Cai T, Luo J and Wei L: KOBAS server: A web-based platform for automated annotation and pathway identification. Nucleic Acids Res. 34:W720–W724. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Lim JH, Kim DJ, Lee DE, Han JY, Chung JH, Ahn HK, Lee SW, Lim DH, Lee YS, Park SY and Ryu HM: Genome-wide microRNA expression profiling in placentas of fetuses with Down syndrome. Placenta. 36:322–328. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Li YY, Alexandrov PN, Pogue AI, Zhao Y, Bhattacharjee S and Lukiw WJ: miRNA-155 up-regulation and complement factor H (CFH) deficits in Down's syndrome. Neuroreport. 23:168–173. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Bofill-De Ros X, Santos M, Vila-Casadesús M, Villanueva E, Andreu N, Dierssen M and Fillat C: Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges. BMC Genomics. 16:9072015. View Article : Google Scholar : PubMed/NCBI

28 

Ben-Ami O, Pencovich N, Lotem J, Levanon D and Groner Y: A regulatory interplay between miR-27a and Runx1 during megakaryopoiesis. Proc Natl Acad Sci USA. 106:238–243. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Izraeli S, Rainis L, Hertzberg L, Smooha G and Birger Y: Trisomy of chromosome 21 in leukemogenesis. Blood Cells Mol Dis. 39:156–159. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Clarimón J, Bertranpetit J, Boada M, Tàrraga L and Comas D: HSP70-2 (HSPA1B) is associated with noncognitive symptoms in late-onset Alzheimer's disease. J Geriatr Psychiatry Neurol. 16:146–150. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Yoo B, Seidl R, Cairns N and Lubec G: Heat-shock protein 70 levels in brain of patients with Down syndrome and Alzheimer's disease. In: The Molecular Biology of Down Syndrome. Springer; New York, NY: pp. 315–322. 1999,

32 

Lockstone HE, Harris LW, Swatton JE, Wayland MT, Holland AJ and Bahn S: Gene expression profiling in the adult Down syndrome brain. Genomics. 90:647–660. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Kahlem P, Sultan M, Herwig R, Steinfath M, Balzereit D, Eppens B, Saran NG, Pletcher MT, South ST, Stetten G, et al: Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of down syndrome. Genome Res. 14:1258–1267. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Pritchard M, Reeves RH, Dierssen M, Patterson D and Gardiner KJ: Down syndrome and the genes of human chromosome 21: Current knowledge and future potentials. Report on the Expert workshop on the biology of chromosome 21 genes: Towards gene-phenotype correlations in Down syndrome. Washington D.C., September 28-October 1, 2007. Cytogenet Genome Res. 121:67–77. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Hibaoui Y, Grad I, Letourneau A, Santoni FA, Antonarakis SE and Feki A: Data in brief: Transcriptome analysis of induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. Genomics Data. 2:226–229. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Shenouda SK and Alahari SK: MicroRNA function in cancer: Oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Sarver AL, Li L and Subramanian S: MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 70:9570–9580. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Perluigi M and Butterfield DA: Oxidative stress and Down syndrome: A route toward Alzheimer-like dementia. Curr Gerontol Geriatr Res. 2012:7249042011.PubMed/NCBI

39 

Pagano G and Castello G: Oxidative stress and mitochondrial dysfunction in Down syndrome. In: Neurodegenerative Diseases. Springer; New York, NY: pp. 291–299. 2012, PubMed/NCBI

40 

Glass R, Townsend-Nicholson A and Burnstock G: P2 receptors in the thymus: Expression of P2X and P2Y receptors in adult rats, an immunohistochemical and in situ hybridisation study. Cell Tissue Res. 300:295–306. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chai M, Su L, Hao X, Zhang M, Zheng L, Bi J, Han X and Gao C: Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome. Mol Med Rep 20: 2063-2072, 2019.
APA
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J. ... Gao, C. (2019). Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome. Molecular Medicine Reports, 20, 2063-2072. https://doi.org/10.3892/mmr.2019.10433
MLA
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J., Han, X., Gao, C."Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome". Molecular Medicine Reports 20.3 (2019): 2063-2072.
Chicago
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J., Han, X., Gao, C."Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome". Molecular Medicine Reports 20, no. 3 (2019): 2063-2072. https://doi.org/10.3892/mmr.2019.10433
Copy and paste a formatted citation
x
Spandidos Publications style
Chai M, Su L, Hao X, Zhang M, Zheng L, Bi J, Han X and Gao C: Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome. Mol Med Rep 20: 2063-2072, 2019.
APA
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J. ... Gao, C. (2019). Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome. Molecular Medicine Reports, 20, 2063-2072. https://doi.org/10.3892/mmr.2019.10433
MLA
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J., Han, X., Gao, C."Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome". Molecular Medicine Reports 20.3 (2019): 2063-2072.
Chicago
Chai, M., Su, L., Hao, X., Zhang, M., Zheng, L., Bi, J., Han, X., Gao, C."Identification of a thymus microRNA‑mRNA regulatory network in Down syndrome". Molecular Medicine Reports 20, no. 3 (2019): 2063-2072. https://doi.org/10.3892/mmr.2019.10433
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