Zhang S, Liu Y D, He Z D, Liu B, Linghu E Q
Department of Gastroenterology, the First Medical Centre of Chinese PLA General Hospital, Beijing 100853, China.
Department of Gastroenterology, the Second Medical Centre of Chinese PLA General Hospital, Beijing 100853, China.
Zhonghua Gan Zang Bing Za Zhi. 2021 Oct 20;29(10):987-994. doi: 10.3760/cma.j.cn501113-20201017-00558.
Differential expression of serum exosomal miRNAs were detected for NAFLD patients and healthy controls, thereby determining the role of serum exosomal miRNAs in the pathogenesis, diagnosis, and treatment of NAFLD. Four patients with S2-3 NAFLD who shared similar demographic features and personal histories, and matched healthy controls were recruited for high-throughput sequencing of serum exosomal miRNAs. Four miRNAs with the most significant differential expression were verified by qRT-PCR in three groups (S1, S2-3, and control groups) with 20 cases in each group. Target gene prediction was performed for these differentially-expressed miRNAs, along with GO and KEGG enrichment analyses for the target genes. T-test or ANOVA were used for normally distributed data. Wilcoxon rank sum test was used for ranked data and non-normally distributed data. The count data used Pearson chi-square test or Fisher's exact test. There were 19 serum exosomal miRNAs with significantly different levels of expression ( < 0.05) and a fold-change > 2. The expression of hsa-miR-122-5p, hsa-miR-146b-5p, and hsa-miR-197-3P was highest in the S2-3 group, followed by the S1 and control groups (in order); hsa-miR-483-3p expression was higher in the NAFLD group (S1 or S2-3) than the control group. There were 84 pathways significantly enriched in target genes. From 20 pathways closely related to NAFLD, at least 5 target genes which were simultaneously correlated to all 10 pathways were screened (PIK3R2, AKT2, AKT3, MAPK1, and NFKB1). Differential expression of serum exosomal miRNAs was detected in NAFLD patients and healthy controls. Four miRNAs with the greatest fold-changes were assessed to judge the severity of fatty degeneration of the liver. The research findings provide reference for non-invasive identification of new biomarkers and specific targets for NAFLD treatment.
检测了非酒精性脂肪性肝病（NAFLD）患者和健康对照者血清外泌体微小RNA（miRNA）的差异表达，从而确定血清外泌体miRNA在NAFLD发病机制、诊断和治疗中的作用。招募了4例具有相似人口统计学特征和个人病史的S2-3期NAFLD患者以及匹配的健康对照者，进行血清外泌体miRNA的高通量测序。对差异表达最显著的4种miRNA在三组（S1组、S2-3组和对照组）中进行qRT-PCR验证，每组20例。对这些差异表达的miRNA进行靶基因预测，并对靶基因进行GO和KEGG富集分析。对正态分布数据采用t检验或方差分析。对排序数据和非正态分布数据采用Wilcoxon秩和检验。计数数据采用Pearson卡方检验或Fisher精确检验。有19种血清外泌体miRNA的表达水平存在显著差异（<0.05）且倍数变化>2。hsa-miR-122-5p、hsa-miR-146b-5p和hsa-miR-197-3P的表达在S2-3组中最高，其次是S1组和对照组（依次排列）；hsa-miR-483-3p在NAFLD组（S1或S2-3）中的表达高于对照组。靶基因中有84条通路显著富集。从与NAFLD密切相关的20条通路中，筛选出至少5个与所有10条通路同时相关的靶基因（PIK3R2、AKT2、AKT3、MAPK1和NFKB1）。在NAFLD患者和健康对照者中检测到血清外泌体miRNA的差异表达。评估了4种倍数变化最大的miRNA，以判断肝脏脂肪变性的严重程度。研究结果为NAFLD治疗新生物标志物的无创鉴定和特异性靶点提供了参考。
