Serum exosomal miRNAs profiling and functional study in patients with non-alcoholic fatty liver disease
10.3760/cma.j.cn501113-20201017-00558
- VernacularTitle:非酒精性脂肪性肝病患者血清外泌体miRNAs表达谱的初步分析和功能研究
- Author:
Shuai ZHANG
1
;
Yingdi LIU
;
Zhandi HE
;
Bo LIU
;
Enqiang LINGHU
Author Information
1. 解放军总医院第一医学中心 消化内科医学部,北京 100853
- Keywords:
Non-alcoholic fatty liver disease;
MicroRNA;
Exosome
- From:
Chinese Journal of Hepatology
2021;29(10):987-994
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.Methods: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.Results:There were 19 serum exosomal miRNAs with significantly different levels of expression ( P < 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). Conclusion: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.