miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

Abstract

Background and objective: This study aimed to identify miRNA as potential diagnostic biomarkers for silicarelated pulmonary fibrosis (SPF). Methods: We first performed a comprehensive miRNAseq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). Results: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10 −3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10 −17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure.Conclusion: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated. † Logistic regression analysis adjusted for age, gender, years of silica dust exposure and pack-years of smoking. miRNA, microRNA; OR, odds ratio; SNP, single nucleotide polymorphism.

Identification of a three-miRNA signature as a novel prognostic model for papillary renal cell carcinoma

“…Although surgery and some replacement therapies including immunotherapy have been widely applied for pRCC patients, the limited response rate and unsatisfied outcomes motivated us to further explore the more appropriate methods to improve the therapeutic With the more distinct advantages of the relatively stable state in tissues and the prominent testability, miR-NAs become increasingly promising to be indicators to forecast prognosis [29,30]. Gluud et al demonstrated the indicating roles of miR-223, miR-191 and miR-342 on therapeutic outcomes of cutaneous T cell lymphomas [31].…”

“…With the more distinct advantages of the relatively stable state in tissues and the prominent testability, miRNAs become increasingly promising to be indicators to forecast prognosis [ 29 , 30 ]. Gluud et al demonstrated the indicating roles of miR-223, miR-191 and miR-342 on therapeutic outcomes of cutaneous T cell lymphomas [ 31 ].…”

MiR‐503 suppresses fibroblast activation and myofibroblast differentiation by targeting VEGFA and FGFR1 in silica‐induced pulmonary fibrosis

“…8 For example, the expression level of miR-4508 from peripheral blood lymphocytes was lower in subjects with silica-related pulmonary fibrosis than that in healthy controls. 9 Elevated expression of miR-7 relieved silica-induced pulmonary fibrosis by blocking epithelial-mesenchymal transition progress. 10 Our previous study also indicated that miR-1224-5p targeted BECN1 to regulate mitochondrial damage in silica-induced pulmonary fibrosis.…”

“…The abnormal expression of miRNAs and the disorder of intracellular signal cascade are closely correlated with the pathological process of pulmonary fibrosis 8 . For example, the expression level of miR‐4508 from peripheral blood lymphocytes was lower in subjects with silica‐related pulmonary fibrosis than that in healthy controls 9 . Elevated expression of miR‐7 relieved silica‐induced pulmonary fibrosis by blocking epithelial‐mesenchymal transition progress 10 .…”

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“…Chu et al . screened workers with silicosis and well‐matched exposed but unaffected controls for differentially expressed micro‐RNA (miRNA) in peripheral blood lymphocytes . miRNA are known to be key regulators of gene transcription which fine tune intracellular mRNA and subsequent protein production.…”