Exposure to nanoparticles may lead to pneumoconiosis and lung cancer; however, whether patients suffering from pneumoconiosis also face a high risk of lung cancer has been under debate for decades. Recently, exosomes have been found to play critical roles in many diseases via intercellular cargo transportation, which has provided a new insight into the mechanistic investigation of nanoparticle-induced respiratory disorders.
Researchers at Zhengzhou University isolated exosomes from the venous blood of patients with pneumoconiosis and healthy controls and then profiled the expression signatures of exosomal miRNAs using high-throughput sequencing technology. A total of 14 aberrantly expressed miRNAs were identified and used to process target gene prediction and functional annotation. Specially, miR-125a along with its target genes EZH2 and hnRNPK was found to play a significant role in the development of lung cancer. The researchers then adopted a series of cellular experiments to validate the role of miR-125a in lung cancer. From the results obtained, they found that the suppression of EZH2 and hnRNPK by high levels of miR-125a inhibited the development of nanoparticle-induced lung adenocarcinoma, which contributed to the clarification of the relation between pneumoconiosis and lung cancer.
Functional re-annotation and enrichment of 14 cancer-related target genes
The functional annotation and enrichment analysis was conducted based on 14 cancer-related target genes; a total of 4 functional groups were identified and shown in different colors, and 5 genes were involved in the miRNA in cancers signaling pathway (A), among which EZH2 and hnRNPK were involved in the pathway and found to be associated with the development of prostate cancer and glioblastoma, respectively (B); thus, the researchers assumed that the inhibition of EZH2 and hnRNPK by miR-125a suppressed the development of lung adenocarcinoma.