# Integrated ceRNA Network Analysis in Silica-Induced Pulmonary Fibrosis and Discovery of miRNA Biomarkers

## TL;DR

This study explores RNA interactions in silicosis and identifies miRNAs that could serve as early diagnostic biomarkers for the disease.

## Contribution

The study discovers miRNA biomarkers and reveals a ceRNA network involved in silicosis pathogenesis.

## Key findings

- Differential expression of mRNAs, lncRNAs, miRNAs, and circRNAs was identified in silicosis mouse models.
- hsa-miR-215-5p and hsa-miR-146b-5p are upregulated in early-stage pneumoconiosis patients and serve as effective diagnostic biomarkers.
- The ceRNA network highlights regulatory interactions in key signaling pathways like PI3K-Akt and NF-κB.

## Abstract

Silicosis is an irreversible and progressive pulmonary fibrotic disease caused by the long-term inhalation of silica dust. The precise molecular mechanisms underlying the disease remain incompletely understood, and effective early diagnostic biomarkers are still lacking. In this study, we used a silicosis mouse model and transcriptomic sequencing to identify 2950 mRNAs, 461 lncRNAs, 81 miRNAs, and 44 circRNAs that were differentially expressed in lung tissue. Enrichment analysis revealed that these differentially expressed genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. The constructed competing endogenous RNA (ceRNA) network highlighted extensive regulatory interactions among lncRNAs/circRNAs, miRNAs, and mRNAs. Human validation showed that the expression levels of hsa-miR-215-5p and hsa-miR-146b-5p were significantly upregulated in the peripheral blood of early-stage pneumoconiosis patients, while hsa-miR-485-5p was downregulated. Logistic regression analysis revealed that hsa-miR-215-5p (OR = 1.966, 95% CI: 1.6938–2.2796, p < 0.001) and hsa-miR-146b-5p (OR = 1.9367, 95% CI: 1.697–2.201, p < 0.001) were independent risk factors for pneumoconiosis (p < 0.001). ROC curve analysis showed that both miRNAs demonstrated good diagnostic efficacy for pneumoconiosis, with AUC values of 0.9563 and 0.8876, respectively. These results provide novel insights into the complex ceRNA regulatory network involved in silicosis pathogenesis and suggest potential early, non-invasive diagnostic biomarkers.