Analysis of microRNA expression profile by small RNA sequencing in Down syndrome fetuses

Xu,Yong; Li,Wuxian; Liu,Xueyan; Ma,Hualin; Tu,Zhiguang; Dai,Yong

doi:10.3892/ijmm.2013.1499

Analysis of microRNA expression profile by small RNA sequencing in Down syndrome fetuses

Authors:
- Yong Xu
- Wuxian Li
- Xueyan Liu
- Hualin Ma
- Zhiguang Tu
- Yong Dai
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Affiliations: Clinical Medical Research Center, Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China, Department of Clinical Laboratory, Chongqing Maternal and Child Health Care Hospital, Chongqing 400013, P.R. China, Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: September 18, 2013 https://doi.org/10.3892/ijmm.2013.1499
Pages: 1115-1125

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Abstract

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and is associated with numerous deleterious phenotypes, including cognitive impairment, childhood leukemia and immune defects. Five Hsa21‑derived microRNAs (i.e., hsa-miR-99a, let-7c, miR-125b-2, miR-155 and miR-802) are involved in variable phenotypes of DS. However, the changes involved in the genome-wide microRNA expression of DS fetuses under the influence of trisomy 21 have yet to be determined. To investigate the expression characteristic of microRNAs during the development of DS fetuses and identify whether another microRNA gene resides in the Hsa21, Illumina high-throughput sequencing technology was employed to comprehensively characterize the microRNA expression profiles of the DS and normal fetal cord blood mononuclear cells (CBMCs). In total, 149 of 395 identified microRNAs were significantly differentially expressed (fold change >2.0 and P<0.001) and 2 of 181 candidate novel microRNAs were identified as residing within the ̔DS critical region̓ of human chromosome 21 (chr21q22.2‑22.3). Additionally, 7 of 14 Hsa21-derived microRNAs were detected, although not all seven were overexpressed in DS CBMCs compared with the control. Gene ontology enrichment analyses revealed that a set of abnormally expressed microRNAs were involved in the regulation of transcription, gene expression, cellular biosynthetic process and nucleic acid metabolic process. Significantly, most of the mRNA targets in these categories were associated with immune modulation (i.e., SOD1, MXD4, PBX1, BCLAF1 and FOXO1). Findings of the present study provided a considerable insight into understanding the expression characteristic of microRNAs in the DS fetal CBMCs. To the best of our knowledge, this is the first study to examine genome-wide microRNA expression profiles in the DS fetus. Differentially expressed microRNAs may be involved in hemopoietic abnormalities and the immune defects of DS fetuses and newborns.

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