A study published in Ecotoxicology and Environmental Safety identified that the circular RNA (circRNA) hsa_circ_0058493 could become a biomarker for diagnosing both idiopathic pulmonary fibrosis (IPF) and silicosis since its knockdown could inhibit the expression of fibrotic molecules in vitro.

Chen et al performed a 4-stage study to identify the possible differentially expressed circRNAs in IPF and silicosis cases compared with those of the corresponding controls. They demonstrated that hsa_circ_0058493 expression was significantly higher in these diseases than in healthy controls, further indicating its use as a potential novel biomarker for IPF and silicosis.

To obtain comprehensive, accurate, and reproducible results, the study used a whole transcriptome sequencing (RNA-seq) strategy and multistage validation designed to assess the association between alternative circRNAs and pulmonary fibrosis.


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“An RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed,” the authors explained. “Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO [GSE102660] dataset (3 IPF cases and 3 controls) and subsequent [quantitative real-time polymerase chain reaction] including 84 additional individuals.” 

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This model revealed that hsa_circ_0058493 expression was mostly increased in the human lung fibroblast cell line (MRC-5) upon previous treatment with transforming growth factor β1. Its “knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process.” the researchers wrote.

The authors wrote, “through a multi-stage study including two main fibrosis-related pulmonary diseases, silicosis and IPF, we identified a circRNA associated with both silicosis and IPF for the first time, which may provide scientific clues for subsequent pulmonary fibrosis mechanism studies.”

Noncoding RNAs, which widely exist in the peripheral blood, are stable and easily obtained through minimally invasive procedures, making them attractive biomarkers for clinical detection. Owing to the covalently closed loop structure without free 3′ or 5′ ends, circRNAs are conferred with high resistance to ribonuclease (RNase) R, rendering them superior to linear RNAs as diagnostic biomarkers.

Pulmonary fibrosis is an end-stage event of various heterogeneous interstitial lung diseases. The basic pathogenic changes in pulmonary fibrosis include inflammation, alveolar epithelial cell injury, the massive proliferation of lung fibroblasts, and abnormalities in lung tissue repair and remodeling, leading to increased morbidity and mortality. In IPF, apparent causes and pathogenic mechanisms are still unknown.

Given their irreversible progression towards fibrosis, it is crucial to reveal the genetic pathogenesis of IPF and silicosis-related pulmonary fibrosis and explore potential biomarkers to screen high-risk groups, predict disease progression, and serve as targets for therapeutic intervention.

Reference

Cheng Z, Zhang Y, Wu S, et al. Peripheral blood circular RNA hsa_circ_0058493 as a potential novel biomarker for silicosis and idiopathic pulmonary fibrosis. Ecotoxicol Environ Saf. Published online April 1, 2022. doi:10.1016/j.ecoenv.2022.113451