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

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

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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.
机译:暴露于纳米颗粒可能导致尘肺和肺癌。然而,数十年来,尘肺病患者是否也面临着肺癌的高风险一直在争论。最近,已发现外来体通过细胞间货物运输在许多疾病中起关键作用,这为纳米颗粒诱发的呼吸系统疾病的机理研究提供了新的见解。本文中,我们从尘肺病患者和健康对照者的静脉血中分离出外泌体,然后使用高通量测序技术分析了外泌体miRNA的表达特征。总共鉴定了14个异常表达的miRNA,并用于处理靶基因预测和功能注释。特别是,发现miR-125a及其靶基因EZH2和hnRNPK在肺癌的发展中起重要作用。然后,我们采用了一系列细胞实验来验证miR-125a在肺癌中的作用。从获得的结果中,我们发现高水平的miR-125a抑制EZH2和hnRNPK抑制了纳米颗粒诱导的肺腺癌的发展,这有助于阐明尘肺与肺癌之间的关系。

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