Down Syndrome and MicroRNAs

Overview

Journal Biomed Rep

Specialty Biochemistry

Date 2018 Feb 7

PMID 29403643

Citations 18

Authors

Aldina Bras

Antonio S Rodrigues

Bruno Gomes

Jose Rueff

Affiliations

Soon will be listed here.

Abstract

In recent years numerous studies have indicated the importance of microRNAs (miRNA/miRs) in human pathology. Down syndrome (DS) is the most prevalent survivable chromosomal disorder and is attributed to trisomy 21 and the subsequent alteration of the dosage of genes located on this chromosome. A number of miRNAs are overexpressed in down syndrome, including miR-155, miR-802, miR- 125b-2, let-7c and miR-99a. This overexpression may contribute to the neuropathology, congenital heart defects, leukemia and low rate of solid tumor development observed in patients with DS. MiRNAs located on other chromosomes and with associated target genes on or off chromosome 21 may also be involved in the DS phenotype. In the present review, an overview of miRNAs and the haploinsufficiency and protein translation of specific miRNA targets in DS are discussed. This aimed to aid understanding of the pathogenesis of DS, and may contribute to the development of novel strategies for the prevention and treatment of the pathologies of DS.

Citing Articles

From Churchill to Elephants: The Role of Protective Genes against Cancer.

Gazzellone A, Sangiorgi E Genes (Basel). 2024; 15(1).

PMID: 38255007 PMC: 10815068. DOI: 10.3390/genes15010118.

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms.

Granholm A J Clin Med. 2023; 12(9).

PMID: 37176630 PMC: 10179128. DOI: 10.3390/jcm12093190.

Genetics and Molecular Basis of Congenital Heart Defects in Down Syndrome: Role of Extracellular Matrix Regulation.

Mollo N, Scognamiglio R, Conti A, Paladino S, Nitsch L, Izzo A Int J Mol Sci. 2023; 24(3).

PMID: 36769235 PMC: 9918028. DOI: 10.3390/ijms24032918.

Upregulation of miR-181a-5p and miR-125b-2-3p in the Maternal Circulation of Fetuses with Rh-Negative Hemolytic Disease of the Fetus and Newborn Could Be Related to Dysfunction of Placental Function.

Xie X, Jiang M, Xiong Z, Huang X Dis Markers. 2022; 2022:2594091.

PMID: 36188428 PMC: 9519318. DOI: 10.1155/2022/2594091.

Advances in molecular characterization of myeloid proliferations associated with Down syndrome.

Li J, Kalev-Zylinska M Front Genet. 2022; 13:891214.

PMID: 36035173 PMC: 9399805. DOI: 10.3389/fgene.2022.891214.

References

Siew W, Tan K, Abbaspour Babaei M, Cheah P, Ling K . MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome. Front Cell Neurosci. 2013; 7:41. PMC: 3625835. DOI: 10.3389/fncel.2013.00041. View

Li Y, Alexandrov P, Pogue A, Zhao Y, Bhattacharjee S, Lukiw W . miRNA-155 upregulation and complement factor H deficits in Down's syndrome. Neuroreport. 2011; 23(3):168-73. PMC: 3264826. DOI: 10.1097/WNR.0b013e32834f4eb4. View

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(5):1115-25. DOI: 10.3892/ijmm.2013.1499. View

Lee Y, Kim M, Han J, Yeom K, Lee S, Baek S . MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004; 23(20):4051-60. PMC: 524334. DOI: 10.1038/sj.emboj.7600385. View

Shaham L, Vendramini E, Ge Y, Goren Y, Birger Y, Tijssen M . MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down syndrome. Blood. 2014; 125(8):1292-301. PMC: 4335082. DOI: 10.1182/blood-2014-06-581892. View

Campos C, Guzman R, Lopez-Fernandez E, Casado A . Urinary uric acid and antioxidant capacity in children and adults with Down syndrome. Clin Biochem. 2009; 43(3):228-33. DOI: 10.1016/j.clinbiochem.2009.09.017. View

Hitzler J, Zipursky A . Origins of leukaemia in children with Down syndrome. Nat Rev Cancer. 2005; 5(1):11-20. DOI: 10.1038/nrc1525. View

Ram G, Chinen J . Infections and immunodeficiency in Down syndrome. Clin Exp Immunol. 2011; 164(1):9-16. PMC: 3074212. DOI: 10.1111/j.1365-2249.2011.04335.x. View

Scott G, Goga A, Bhaumik D, Berger C, Sullivan C, Benz C . Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 2006; 282(2):1479-86. DOI: 10.1074/jbc.M609383200. View

10.

Creutzig U, Ritter J, Vormoor J, Ludwig W, Niemeyer C, Reinisch I . Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia. 1996; 10(11):1677-86. View

11.

Alexandrov P, Percy M, Lukiw W . Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down's Syndrome and Trisomy-21 Linked Disease. Cell Mol Neurobiol. 2017; 38(3):769-774. PMC: 5756687. DOI: 10.1007/s10571-017-0514-0. View

12.

Nguyen L, Lepleux M, Makhlouf M, Martin C, Fregeac J, Siquier-Pernet K . Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology. Mol Autism. 2016; 7:1. PMC: 4705753. DOI: 10.1186/s13229-015-0064-6. View

13.

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J . The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956):415-9. DOI: 10.1038/nature01957. View

14.

Bras A, Monteiro C, Rueff J . Oxidative stress in trisomy 21. A possible role in cataractogenesis. Ophthalmic Paediatr Genet. 1989; 10(4):271-7. DOI: 10.3109/13816818909009882. View

15.

Raoul O, Carpentier S, Dutrillaux B, Mallet R, LeJeune J . [Partial trisomy of chromosome 21 by maternal translocation t(15;21) (q26.2; q21)]. Ann Genet. 1976; 19(3):187-90. View

16.

Keck-Wherley J, Grover D, Bhattacharyya S, Xu X, Holman D, Lombardini E . Abnormal microRNA expression in Ts65Dn hippocampus and whole blood: contributions to Down syndrome phenotypes. Dev Neurosci. 2011; 33(5):451-67. PMC: 3254042. DOI: 10.1159/000330884. View

17.

Wang P, Sun Y, Zhang S, Pang M, Zhang H, Gao S . Let-7c inhibits A549 cell proliferation through oncogenic TRIB2 related factors. FEBS Lett. 2013; 587(16):2675-81. DOI: 10.1016/j.febslet.2013.07.004. View

18.

Svobodova I, Korabecna M, Calda P, Brestak M, Pazourkova E, Pospisilova S . Differentially expressed miRNAs in trisomy 21 placentas. Prenat Diagn. 2016; 36(8):775-84. DOI: 10.1002/pd.4861. View

19.

Billet S, Aguilar F, Baudry C, Clauser E . Role of angiotensin II AT1 receptor activation in cardiovascular diseases. Kidney Int. 2008; 74(11):1379-84. DOI: 10.1038/ki.2008.358. View

20.

Lim J, Kim D, Lee D, Han J, Chung J, Ahn H . Genome-wide microRNA expression profiling in placentas of fetuses with Down syndrome. Placenta. 2015; 36(3):322-8. DOI: 10.1016/j.placenta.2014.12.020. View