Genome-wide analysis of aberrantly expressed circulating miRNAs in patients with coal workers’ pneumoconiosis

摘要

Emerging evidence indicates that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, have important roles in multiple biological processes. To determine the potential contribution of miRNAs to coal workers’ pneumoconiosis (CWP), we comprehensively surveyed and identified differentially expressed miRNA profiles in patients with CWP by small RNA sequencing and analysis. Mixed serum samples from the different stages of CWP and the control samples were subjected to deep sequencing by applying next-generation sequencing technology. Samples at different disease stages exhibited inconsistent miRNA expression profiles and differentially expressed miRNA profiles. Generally, these miRNAs were dynamically expressed across the different disease stages and showed various relative expression levels. Some miRNAs (such as miR-18a*, 149, 222 and 671-3p) were consistently up-regulated or down-regulated in the different stages of CWP samples. Most of the aberrantly expressed miRNAs showed a down-regulation trend. Differentially expressed miRNAs were also subjected to pairwise comparison between the different stages. Some miRNAs showed significant inconsistent expression trends across the three stages, although they were not significantly dysregulated based on the control sample. Furthermore, a series of special miRNAs organized into miRNA gene clusters and gene families were also surveyed for aberrant expression (such as mir-200 gene family and mir-222 gene cluster). According to experimentally validated target mRNAs of the aberrantly and abundantly expressed miRNAs, functional enrichment analysis suggests that these miRNAs play important roles in various biological processes, including lung tumorigenesis. In summary, we demonstrated that aberrantlyexpressed circulating miRNAs showed dynamic expression patterns across diseased samples, which suggests that these miRNAs may have critical roles in the occurrence and development of CWP. In addition, some significantly dysregulated miRNAs may be potential non-invasive diagnosis biomarkers based on further study.