Li Shuangshuang, Wang Shiqi, Guo Zhenhua, Wu Huan, Jin Xianqing, Wang Yi, Li Xiaoqing, Liang Shaoyan
Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.
Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
PLoS One. 2016 Mar 2;11(3):e0150222. doi: 10.1371/journal.pone.0150222. eCollection 2016.
Hirschsprung's disease (HSCR), the most common congenital malformation of the gut, is regulated by multiple signal transduction pathways. Several components of these pathways are important targets for microRNAs (miRNAs). Multiple miRNAs have been associated with the pathophysiology of HSCR, and serum miRNAs profiles of HSCR patients have been reported, but miRNA expression in HSCR colon tissue is almost completely unexplored. Using microarray technology, we screened colon tissue to detect miRNAs whose expression profiles were altered in HSCR and identify targets of differentially expressed miRNAs. Following filtering of low-intensity signals, data normalization, and volcano plot filtering, we identified 168 differentially expressed miRNAs (104 up-regulated and 64 down-regulated). Fifty of these mRNAs represent major targets of dysegulated miRNAs and may thus important roles in the pathophysiology of HSCR. Pathway analysis revealed that 7 of the miRNA targets encode proteins involved in regulation of cell proliferation and migration via RET and related signaling pathways (MAPK and PI3K/AKT). Our results identify miRNAs that play key roles in the pathophysiology of the complex multi-factorial disease HSCR.
先天性巨结肠（HSCR）是最常见的肠道先天性畸形，受多种信号转导通路调控。这些通路的几个组成部分是微小RNA（miRNA）的重要作用靶点。多种miRNA与HSCR的病理生理学相关，并且已有关于HSCR患者血清miRNA谱的报道，但HSCR结肠组织中的miRNA表达几乎完全未被研究。我们利用微阵列技术筛选结肠组织，以检测其表达谱在HSCR中发生改变的miRNA，并鉴定差异表达miRNA的靶标。经过低强度信号过滤、数据归一化和火山图过滤后，我们鉴定出168个差异表达的miRNA（104个上调和64个下调）。其中50个mRNA代表失调miRNA的主要靶标，因此可能在HSCR的病理生理学中发挥重要作用。通路分析显示，7个miRNA靶标编码通过RET及相关信号通路（MAPK和PI3K/AKT）参与细胞增殖和迁移调控的蛋白质。我们的研究结果鉴定出在复杂多因素疾病HSCR的病理生理学中起关键作用的miRNA。
