Children's Hospital of Soochow University, Suzhou, P.R. China.
Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, P.R. China.
J Cell Biochem. 2018 Nov;119(10):8195-8203. doi: 10.1002/jcb.26830. Epub 2018 Apr 6.
Hirschsprung's disease (HSCR) is a birth defect that causes a failure of the enteric nervous system to cover the distal gut during early embryonic development. Evidence shows that long non-coding RNAs (lncRNA) play important roles in HSCR. The MIR31 host gene (MIR31HG), also known as Loc554202, is a long non-coding RNA (lncRNA), which acts as the host gene of (microRNA) miR-31 and miR-31*. There have been no studies regarding its function in early developmental defects during pregnancy, and its downstream genetic receptors. We report that downregulation of MIR31HG inhibited migration and proliferation in 293T and SH-SY5Y cell lines, by suppressing miR-31 and miR-31*. Moreover, the downregulation of miR-31 and miR-31* enhanced inter-α-trypsin inhibitor heavy chain 5 (ITIH5) and the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic gamma subunit (PIK3CG), respectively with reductions of cell migration and proliferation in 293T and SH-SY5Y cell lines. In addition, synergistic actions were observed between miR-31 and miR-31* in cell migration and proliferation. Our results demonstrated that the MIR31HG-miR-31/31*-ITIH5/PIK3CG pathway plays a role in the pathogenesis of HSCR.
先天性巨结肠（HSCR）是一种出生缺陷，导致在胚胎早期发育过程中肠神经系统未能覆盖远端肠道。有证据表明，长链非编码 RNA（lncRNA）在 HSCR 中发挥重要作用。MIR31 宿主基因（MIR31HG），也称为 Loc554202，是一个长链非编码 RNA（lncRNA），作为 microRNA（miR-31 和 miR-31*）的宿主基因。目前尚无关于其在妊娠早期发育缺陷及其下游遗传受体中的功能的研究。我们报告下调 MIR31HG 通过抑制 miR-31 和 miR-31抑制 293T 和 SH-SY5Y 细胞系的迁移和增殖。此外，下调 miR-31 和 miR-31分别增强了α-胰蛋白酶抑制剂重链 5（ITIH5）和磷脂酰肌醇-4,5-二磷酸 3-激酶催化γ亚基（PIK3CG），导致 293T 和 SH-SY5Y 细胞系的迁移和增殖减少。此外，miR-31 和 miR-31在细胞迁移和增殖中观察到协同作用。我们的结果表明，MIR31HG-miR-31/31-ITIH5/PIK3CG 通路在 HSCR 的发病机制中起作用。
