Lu Chao, Wei Furong, He Xinjue, Yao Xin, Yu Chaohui
Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Open Med (Wars). 2022 Apr 12;17(1):732-740. doi: 10.1515/med-2022-0473. eCollection 2022.
Idiopathic achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES). However, the pathogenesis of idiopathic achalasia remains unclear. To further understand the pathogenesis, we conducted lncRNA and mRNA microarray analyses. LES specimens from 5 patients and 4 controls were used for microarray. Potential target genes with significantly changed lncRNA and mRNA were predicted using cis/trans-regulatory algorithms, followed by the Gene Ontology and KEGG pathway enrichment analysis to understand the biophysical effect. Finally, 7,133 significantly dysregulated mRNAs (3,136 increased and 3,997 decreased), along with 6,892 significantly dysregulated lncRNAs (4,900 increased and 1,992 decreased). Biophysical function analysis revealed that the cell adhesion molecule (CAM) pathway was a common pathway. The predicted lncRNA targets of NRXN1 (Down FC: 9.07), NTNG2 (UP FC: 2.75), CADM1 (Down FC: 2.26), NLGN1 (Down FC: 4.60), NEGR1 (Down FC: 2.335), CD22 (Down FC: 5.62), HLA-DQB1 (Down FC: 5.06), and HLA-DOA (Down FC: 2.31) were inputted in this pathway, which was mainly located in the synapse part of the neural system and immune system. Our study demonstrates the lncRNAs and corresponding mRNAs that may play important roles in idiopathic achalasia.
特发性贲门失弛缓症是一种原发性食管动力障碍性疾病，其特征为食管蠕动缺失以及食管下括约肌（LES）松弛受损。然而，特发性贲门失弛缓症的发病机制仍不清楚。为了进一步了解其发病机制，我们进行了长链非编码RNA（lncRNA）和信使核糖核酸（mRNA）微阵列分析。使用5例患者和4例对照的LES标本进行微阵列分析。使用顺式/反式调控算法预测lncRNA和mRNA显著变化的潜在靶基因，随后进行基因本体论和京都基因与基因组百科全书（KEGG）通路富集分析以了解生物物理效应。最终，共发现7133个显著失调的mRNA（3136个上调和3997个下调），以及6892个显著失调的lncRNA（4900个上调和1992个下调）。生物物理功能分析显示，细胞黏附分子（CAM）通路是一条共同通路。将神经细胞黏附分子1（NRXN1，下调倍数变化：9.07）、神经生长导向因子2（NTNG2，上调倍数变化：2.75）、细胞黏附分子1（CADM1，下调倍数变化：2.26）、神经连接蛋白1（NLGN1，下调倍数变化：4.60）、神经生长相关蛋白1（NEGR1，下调倍数变化：2.335）、白细胞分化抗原22（CD22，下调倍数变化：5.62）、人组织相容性复合体Ⅱ类分子DQβ1（HLA-DQB1，下调倍数变化：5.06）和人组织相容性复合体Ⅱ类分子DOα（HLA-DOA，下调倍数变化：2.31）的预测lncRNA靶标输入该通路，该通路主要位于神经系统和免疫系统的突触部分。我们的研究证明了lncRNA和相应的mRNA可能在特发性贲门失弛缓症中发挥重要作用。
