Zeng Jiahang, Liu Wei, Liang Jianhua, Peng Junzheng, Wang Fenghua, Tang Jue, Yang Qinglin, Zhuang Linwei, Huang Dongmei, Li Le
Department of Thoracic Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Pediatr. 2021 Nov 18;9:671107. doi: 10.3389/fped.2021.671107. eCollection 2021.
Specific diagnostic markers for congenital pulmonary airway malformations (CPAMs) have not yet been discovered. This study intends to detect differentially expressed miRNAs in type I and type II CPAMs by using a miRNA chip and clarify the feasibility of miRNAs as different CPAM typing markers. Lung tissues of type I and type II CPAMs were collected and used to assess the differentially expressed miRNAs using a miRNA chip after evaluation using hematoxylin-eosin staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction and fluorescence in situ hybridization were used to verify the quality of the miRNA chip. The function and pathways of related differentially expressed miRNAs were analyzed by Gene Ontology Enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Targets of miRNAs were predicted by targetscan7.1 and mirdbV6 and the network between miRNA and mRNA was established using Cystoscope software. In total, 394/34 upregulated and 321/72 downregulated miRNAs were found in type I and type II CPAMs, respectively. GO and KEGG analysis showed that different pathways are involved in the regulation of CPAM, including platelet activation, Ras, MAPK, FoxO, and PI3K-Akt signaling pathways. miRNA-mRNA network analysis confirmed four major miRNAs in CPAM, including miR-4731-5p to complexin 2, miR-3150a-3p to vesicle amine transport 1, miR-32-5p to F-box and WD repeat domain containing 7, and miR-454-3p to SLAIN motif family member 1. In summary, we have identified four candidate miRNAs and pathways related to different pattern CPAMs, which provide a new perspective for CPAM research and treatment.
先天性肺气道畸形（CPAMs）的特异性诊断标志物尚未被发现。本研究旨在通过使用miRNA芯片检测I型和II型CPAMs中差异表达的miRNA，并阐明miRNA作为不同CPAM分型标志物的可行性。收集I型和II型CPAMs的肺组织，在苏木精-伊红染色和Masson染色评估后，使用miRNA芯片评估差异表达的miRNA。采用定量逆转录-聚合酶链反应和荧光原位杂交验证miRNA芯片的质量。分别通过基因本体论富集（GO）分析和京都基因与基因组百科全书（KEGG）分析对相关差异表达miRNA的功能和途径进行分析。通过targetscan7.1和mirdbV6预测miRNA的靶标，并使用Cystoscope软件建立miRNA与mRNA之间的网络。总共在I型和II型CPAMs中分别发现394/34个上调和321/72个下调的miRNA。GO和KEGG分析表明，不同的途径参与CPAM的调控，包括血小板活化、Ras、MAPK、FoxO和PI3K-Akt信号通路。miRNA-mRNA网络分析确定了CPAM中的四个主要miRNA，包括与突触结合蛋白2结合的miR-4731-5p、与囊泡胺转运体1结合的miR-3150a-3p、与含F-box和WD重复结构域7结合的miR-32-5p以及与SLAIN基序家族成员1结合的miR-454-3p。总之，我们已经鉴定出与不同模式CPAMs相关的四个候选miRNA和途径，这为CPAM的研究和治疗提供了新的视角。
