变应性鼻炎患者鼻黏膜微小RNA的表达谱及其意义

Analysis of microRNA expression profiles in allergic rhinitis

目的探讨变应性鼻炎(AR)患者鼻黏膜微小RNAs(miRNAs)的表达谱特点,阐明miRNAs在AR的发病、诊断及治疗中的作用。方法研究设AR组及非变应性鼻炎患者(对照组),对其鼻黏膜进行总RNA抽提,应用RNA-seq技术对鼻黏膜miRNA进行差异表达谱的分析。利用芯片技术,对miRNA进行二级结构的预测,从而判断和预测新的miRNA。比较2组新预测的miRNA的异常表达,筛选其miRNA,构建AR的新预测miRNA异常表达谱。结果将所有序列与rfam数据库进行比对,得到其中miRNA的具体分布情况。通过miRNA芯片,检测共有172个新预测的miRNA在2组鼻黏膜组织中表达,而AR组标本中表达的miRNA共有351个,有84个预测的miRNA在AR组共同表达。在对照组样品中表达的有342个,有85个预测的miRNA在对照组共同表达。本研究数据得到的6个新预测的miRNA在样本间差异表达(P<0.05)。对于得到的新预测的miRNA,使用软件miRand、RNAhybrid预测其靶基因。以新预测的128883为例,其对应的miRNA靶基因为34个。差异表达miRNA靶基因富集,得到差异表达新的miRNA与8条通路有关,分别是轴突指导、突触小泡循环、急性髓性白血病、胞吞作用、ErbB信号通路、Ras信号通路、黑色素瘤和赖氨酸降解。结论变应性鼻炎患者涉及多个新预测的miRNA,以及不同的信号通路,可能为AR患者的发病机制的研究提供新的思路。

Objective To investigate the expression profiles of microRNAs(miRNAs) in nasal mucosa of patients with allergic rhinitis(AR), and to elucidate the role of miRNAs in the pathogenesis, diagnosis and treatment of AR. Methods Total RNA was extracted from nasal mucosa of patients with variant rhinitis(AR group) and non-variant rhinitis(control group). RNA-aeq technique was used to analyze differential express profile of miRNAs between the two groups. Using chip technology, the new miRNA was predicted by the Dicer enzyme binding site and the free energy of its secondary structure. The abnormal expression of newly predicted miRNAs in the AR and control groups were compared, and aberrant expression of miRNAs were screened in the newly predicted miRNAs to construct a new predicted miRNA abnormal expression profile of allergic rhinitis. Results All sequences were aligned with the rfam database to obtain distributions of sRNAs such as miRNA, rRNA, scRNA, snoRNA, snRNA and tRNA. A total of 172 newly predicted miRNAs were detected in the two groups by miRNA microarray, while 351 miRNA were expressed in the AR group and 84 predicted miRNAs were co-expressed in the AR group. 342 miRNAs were expressed in the control group, and 85 predicted miRNAs were co-expressed in the control group. The six newly predicted miRNAs obtained from this study were differentially expressed(P<0.05). For the newly predicted miRNAs obtained, the target genes were predicted using the software miRand and RNAhybrid. Taking the newly predicted 128883 as an example, the corresponding miRNA target genes were 34. Differential expression of miRNA target gene was enriched, the differential expression of new miRNAs was associated with eight pathways, including axon guidance, synaptic vesicle cycle, acute myeloid leukemia, cytosis, ErbB signaling pathway, RAS signaling pathway, melanoma and lysine degradation. Conclusion Patients with variant rhinitis involve multiple newly predicted miRNAs, as well as different signal transduction pathways, which may provide new ideas for the study of the pathogenesis of patients with rhinitis.