先天性巨结肠中lncRNA-CARMN调控ARP2/3复合体致肠神经嵴细胞迁移增殖障碍的分子机制研究

先天性巨结肠是小儿常见的先天性消化道畸形之一，该病由于胚胎期肠神经嵴细胞迁移障碍所致。研究表明，非编码RNA参与众多病理过程，而lnc-CARMN参与胚胎发育及癌症的转移，与迁移密切相关，但尚未在先天性巨结肠中得到其功能的印证。CARMN的内含子区可编码miR-145，miR-145已证实可参与胚胎发育及细胞迁移，但尚未在先天性巨结肠中明确其功能。结合生物信息学预测，miR-145可同时调控ARP2/3复合体的两个亚基，即ACTR2、ACTR3。ARP2/3复合体作为新生肌丝的起点，与细胞骨架的功能息息相关，参与细胞迁移。由人群样本结合细胞培养，验证lnc-CARMN--miR-45—ARP2/3 复合体通路在先天性巨结肠发病机制中的功能。

Hirschsprung's disease is one of the common congenital malformations of the digestive tract in children. The disease is caused by the migration disorder of the enteric nerve crest cells in the embryonic stage. Studies have shown that non-coding RNA is involved in many pathological processes, and lnc-CARMN is involved in embryonic development and cancer metastasis, and is closely related to migration, but its function has not been confirmed in Hirschsprung's disease. The intron region of CARMN can encode miR-145, which has been confirmed to be involved in embryonic development and cell migration, but its function has not been clarified in Hirschsprung's disease. Combined with bioinformatics predictions, miR-145 can simultaneously regulate the two subunits of the ARP2/3 complex, namely ACTR2 and ACTR3. ARP2/3 complex, as the starting point of new myofilament, is closely related to the function of the cytoskeleton and participates in cell migration. Combining human samples with cell culture to verify the function of the lnc-CARMN-miR-45-ARP2/3 complex pathway in the pathogenesis of Hirschsprung's disease.