Genome-wide analysis of aberrantly expressed microRNAs in bronchoalveolar lavage fluid from patients with silicosis

Abstract

Background To identify differentially expressed miRNAs profiles in bronchoalveolar lavage fluid (BALF) from patients with silicosis and consider the potential contribution of miRNAs to silicosis.Methods miRNAs expression profiling were performed in the cell fraction of BALF samples obtained from 9 subjects (3 silicosis observation subjects, 3 stage I and stage II silicosis patients, respectively). The differential expression of two selected miRNAs hsa-miR-181c-5p and hsa-miR-29a-3p were confirmed by RT-qPCR. Furthermore, miRNAs Gene Ontology Enrichment categories and target mRNAs were determined based on miRWalk.Results We found 110 dysregulated miRNAs in silicosis samples, most of which showed a down-regulation trend. Microarray results were confirmed by RT-qPCR. With the observation group samples set as standards, stage I samples showed 123 differentially expressed miRNAs, and stage II 46. 23 miRNAs were dysregulated in both stages. Finally, functional enrichment analysis indicated that these miRNAs played an important role in various biological processes, including ECM-receptor interaction and endocytosis.Conclusions This is the first time to acquire the BALF-derived microRNAs expression profiling targeting to human silicosis. These results contribute to unravelling miRNAs involved in the pathogenesis of silicosis, and provide new tools of potential use of as biomarkers for diagnosis and/or therapeutic purposes.

Upregulated miR-29c suppresses silica-induced lung fibrosis through the Wnt/β-catenin pathway in mice

“…According to the published data, miR-29 is a major regulator of genes associated with lung fibrosis, and the downregulation of miR-29 expression could be associated with the pathophysiology of silicosis. 1 Thus, a lentiviral vector was constructed, named Lv-miR-29c, to investigate the molecular mechanism of miR-29c in the development of silicosis using a mouse silicosis model. Wnt/-catenin signaling pathway is involved in the development of silicosis, and -catenin is a key regulator in this procession.…”

“…Silicosis is an irreversible lung disease with pulmonary diffuse fibrosis as main manifestation resulting from long-term inhalation of occupational dust containing silicon dioxide (SiO 2 ). 1 Meanwhile, it is one of the most common and severe occupational diseases with no effective treatment, being caused by excessive epithelial injury, the formation of fibroblastic foci, extracellular matrix (ECM) accumulation, and epithelial-mesenchymal transition (EMT). 2 However, the pathogenesis of silicosis has not been clearly understood yet.…”

Dynamic assessing silica particle-induced pulmonary fibrosis and associated regulation of long non-coding RNA expression in Wistar rats

“…Silicosis is an irreversible lung disease with pulmonary diffuse fibrosis as main manifestation resulting from long-term inhalation of occupational dust containing silica particles [ 1 ]. During the recent outbreaks of silicosis across Australia since 2015, about 350 silicosis patients have been diagnosed, and many were characterized as accelerated silicosis (AS) which is more rapidly progressive than traditional chronic silicosis [ 2 ].…”

PTEN Hypomethylation Could Be A Biomarker For Early Detection of Silicosis

“…Dysregulated mRNAs and miRNAs associated with silica-induced pulmonary brosis, pneumoconiosis, or silicosis were reported in previous studies [14,[23][24][25][26][27], but the exact identify of differential mRNA and miRNA expression remains to be completely elucidated. Based on silicosis rats model, 39 altered miRNAs were identi ed involving in lung brosis [10]; based on silicosis patients bronchoalveolar lavage uid (BALF) samples, there were 110 dysregulated miRNAs, and different stages of silicosis were associated with distinct changes in miRNAs expression [4]; whereas our results showed 1417 and 241 differentially expressed mRNAs and miRNAs, respectively, and most mRNAs or miRNAs expressions had no signi cant difference between early stage and advanced stage silicosis lung tissues. The above differences might possibly be explained by miRNA high conservation, species diversity, and sample size expansion [10].…”

“…Besides, dysregulated mRNAs and miRNAs are implicated in immune response and in ammation [3], and differences in mRNAs and miRNAs expressions between silicosis and normal subjects have been reported in many studies [4][5][6][7][8][9][10]. However, most subjects of current silicosis related transcriptome studies concentrate mainly on human blood [6,7], bronchoalveolar lavage uid [4], macrophages [9], lung epithelial cells [8], or rats model [10][11][12] instead of silica dust major target organ-human lung tissue. In addition, despite the same silicosis rats model, the numbers of differential mRNA or miRNA expression were still controversial [5,10,13,14].…”