Up-regulation of exosomal miR-125a in pneumoconiosis inhibits lung cancer development by suppressing expressions of EZH2 and hnRNPK

尘肺病中外泌体 miR-125a 的上调通过抑制 EZH2 和 hnRNPK 的表达来抑制肺癌的发展

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作者:Lin Zhang, Jiangfeng Li, Changfu Hao, Wei Guo, Di Wang, Jianhui Zhang, Youliang Zhao, Shuyin Duan, Wu Yao

Abstract

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. Herein, we isolated exosomes from the venous blood of patients with pneumoconiosis and healthy controls and then, we 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. We then adopted a series of cellular experiments to validate the role of miR-125a in lung cancer. From the results obtained, we 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.

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