Department of Pediatrics, Nanjing Maternal and Child Health Hospital Affiliated of Nanjing Medical University, Nanjing, PR China.
Int J Mol Med. 2012 Jan;29(1):53-60. doi: 10.3892/ijmm.2011.797. Epub 2011 Sep 20.
microRNAs (miRNAs) have emerged as key regulators in many biological processes, particularly cardiac growth and development, although the specific miRNA expression profile associated with this process remains to be elucidated. This study aimed to characterize the cellular microRNA profile involved in the development of congenital heart malformation, through the investigation of single ventricle (SV) defects. Comprehensive miRNA profiling in human fetal SV cardiac tissue was performed by deep sequencing. Differential expression of 48 miRNAs was revealed by sequencing by oligonucleotide ligation and detection (SOLiD) analysis. Of these, 38 were down-regulated and 10 were up-regulated in differentiated SV cardiac tissue, compared to control cardiac tissue. This was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Predicted target genes of the 48 differentially expressed miRNAs were analyzed by gene ontology and categorized according to cellular process, regulation of biological process and metabolic process. Pathway-Express analysis identified the WNT and mTOR signaling pathways as the most significant processes putatively affected by the differential expression of these miRNAs. The candidate genes involved in cardiac development were identified as potential targets for these differentially expressed microRNAs and the collaborative network of microRNAs and cardiac development related-mRNAs was constructed. These data provide the basis for future investigation of the mechanism of the occurrence and development of fetal SV malformations.
微小 RNA(miRNAs)已成为许多生物学过程的关键调节因子,特别是心脏的生长和发育,尽管与这一过程相关的特定 miRNA 表达谱仍有待阐明。本研究旨在通过研究单心室(SV)缺陷,描述与先天性心脏畸形发育相关的细胞 miRNA 特征。通过深度测序对人胎儿 SV 心脏组织中的 miRNA 进行了全面的 miRNA 谱分析。通过寡核苷酸连接和检测(SOLiD)分析显示,48 个 miRNA 的表达存在差异。与对照心脏组织相比,分化的 SV 心脏组织中 38 个下调,10 个上调。通过实时定量逆转录聚合酶链反应(qRT-PCR)分析证实了这一点。对 48 个差异表达 miRNA 的预测靶基因进行了基因本体分析,并根据细胞过程、生物过程调节和代谢过程进行了分类。Pathway-Express 分析确定 WNT 和 mTOR 信号通路是这些 miRNA 差异表达可能影响的最重要的过程。鉴定出与心脏发育相关的候选基因作为这些差异表达 miRNA 的潜在靶基因,并构建了 miRNA 和心脏发育相关-mRNA 的协同网络。这些数据为进一步研究胎儿 SV 畸形发生和发展的机制提供了基础。