Li Qi, Peng Xiaohong, Huang Haoran, Li Jingjing, Wang Fan, Wang Jie
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Medicine (Baltimore). 2017 Nov;96(47):e8837. doi: 10.1097/MD.0000000000008837.
This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs). The target genes of the DEMs were predicted using the online tool miRWalk, which were then mapped to DAVID (https://david.ncifcrf.gov/) for functional annotation based on GO database and for pathway enrichment analysis based on KEGG. Finally, a miRNA-target-protein-protein interaction (PPIs) network was constructed using the DEMs and their target genes with interaction.Differential expression analysis reveals 24 DEMs between the SSNHL group and control group. A total of 1083 target genes were predicted. GO functional annotation analysis reveals that the target genes in the top 10 terms are mainly related to the development of salivary glands, neurotransmission, dendritic development, and other processes. KEGG pathway enrichment analysis reveals that the target genes were functionally enriched in pathways arachidonic acid metabolism, complement and coagulation cascades, linoleic acid metabolism, and MAPK signaling pathway. In the miRNA-target-PPI network, hsa-miR-34a/548n/15a/143/23a/210/1255a/18b/ /1180/99b had the most target genes; genes YWHAG, GSK3B, CDC42, NR3C1, LCK, UNC119, SIN3A, and NFKB2, interact with most other genes among all the predicted target genes.Hsa-miR-34a/15a/23a/210/18b/548n/143 is likely to have a role in the pathogenesis of SSNHL.
本研究旨在通过RNA测序(RNA-seq)鉴定可能与突发性感音神经性听力损失(SSNHL)发病机制相关的微小RNA(miRNA)。分别从SSNHL患者和健康志愿者中提取RNA。在HiSeq4000平台上进行测序。过滤后,将干净的 reads 映射到人类参考基因组 hg19。使用DEseq对SSNHL样本和正常样本之间的miRNA进行差异表达分析,以鉴定差异表达的微小RNA(DEM)。使用在线工具miRWalk预测DEM的靶基因,然后将其映射到DAVID(https://david.ncifcrf.gov/)进行基于GO数据库的功能注释和基于KEGG的通路富集分析。最后,使用具有相互作用的DEM及其靶基因构建miRNA-靶标-蛋白质-蛋白质相互作用(PPI)网络。差异表达分析显示SSNHL组和对照组之间有24个DEM。共预测了1083个靶基因。GO功能注释分析显示,前10个术语中的靶基因主要与唾液腺发育、神经传递、树突发育等过程相关。KEGG通路富集分析显示,靶基因在花生四烯酸代谢、补体和凝血级联、亚油酸代谢和MAPK信号通路中功能富集。在miRNA-靶标-PPI网络中,hsa-miR-34a/548n/15a/143/23a/210/1255a/18b//1180/99b具有最多的靶基因;在所有预测的靶基因中,基因YWHAG、GSK3B、CDC42、NR3C1、LCK、UNC119、SIN3A和NFKB2与大多数其他基因相互作用。Hsa-miR-34a/15a/23a/210/18b/548n/143可能在SSNHL的发病机制中起作用。