Clinical Medical Research Center, Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China.
Int J Mol Med. 2013 Nov;32(5):1115-25. doi: 10.3892/ijmm.2013.1499. Epub 2013 Sep 18.
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.
唐氏综合征（DS）是由人类 21 号染色体（Hsa21）三体引起的，与许多有害表型有关，包括认知障碍、儿童白血病和免疫缺陷。五种 Hsa21 衍生的 microRNAs（即 hsa-miR-99a、let-7c、miR-125b-2、miR-155 和 miR-802）参与了 DS 的多种表型。然而，在 21 三体的影响下，DS 胎儿全基因组 microRNA 表达的变化仍有待确定。为了研究 DS 胎儿发育过程中 microRNA 的表达特征，以及是否存在另一个 microRNA 基因位于 Hsa21 上，我们采用 Illumina 高通量测序技术全面描绘了 DS 和正常胎儿脐血单个核细胞（CBMC）的 microRNA 表达谱。总共鉴定出 395 个 microRNAs 中有 149 个显著差异表达（倍数变化>2.0，P<0.001），181 个候选新 microRNAs 中有 2 个被鉴定为位于人类染色体 21 的“DS 关键区域”（chr21q22.2-22.3）内。此外，在 DS CBMC 中检测到了 14 个 Hsa21 衍生的 microRNAs 中的 7 个，但并非所有 7 个在 DS CBMC 中都比对照过度表达。基因本体富集分析显示，一组异常表达的 microRNAs 参与了转录、基因表达、细胞生物合成过程和核酸代谢过程的调控。重要的是，这些类别中的大多数 mRNA 靶标与免疫调节有关（即 SOD1、MXD4、PBX1、BCLAF1 和 FOXO1）。本研究的结果为深入了解 DS 胎儿 CBMC 中 microRNAs 的表达特征提供了重要线索。据我们所知，这是首次研究 DS 胎儿全基因组 microRNA 表达谱。差异表达的 microRNAs 可能参与 DS 胎儿和新生儿的造血异常和免疫缺陷。
