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暴露于α辐射的BEAS - 2B细胞中的微小RNA分析揭示了恶性细胞转化的潜在生物标志物。

MicroRNA profiling in BEAS-2B cells exposed to alpha radiation reveals potential biomarkers for malignant cellular transformation.

作者信息

Dang Xuhong, Lin Haipeng, Li Youchen, Guo Xiuli, Yuan Yayi, Zhang Ruifeng, Li Xiaozhen, Chai Dongliang, Zuo Yahui

机构信息

Division of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China.

Department of Pathology, Shanxi Provincial Cancer Hospital, Taiyuan 030013, China.

出版信息

Toxicol Res (Camb). 2020 Dec 12;9(6):834-844. doi: 10.1093/toxres/tfaa094. eCollection 2020 Dec.

Abstract

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. The risk of lung cancer from radon exposure is due to the continuous radioactive decay of this gas and subsequent emission of high-energy alpha decay particles. And the bronchial epithelial cells are the main targets of radon exposure. However, there is a lack of early warning indicators of lung cancer caused by radon in the physical examination of populations involved in occupations with higher exposure to radon. To assess the potential of a molecular-based marker approach for the early detection of human lung cancer induced by radon, human bronchial epithelial cell injury models induced by alpha-particle irradiation were constructed. The results of transwell migration assay, transwell invasion assay, and the expression of the epithelial-mesenchymal transition-related proteins showed that malignant cell transformation could be triggered by alpha irradiation. Potential microRNAs (miRNAs) (hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257) were screened using miRNA chips in cell models. The pathway analyses of miRNAs selected using DIANA-miRPath v3.0 showed that miRNAs involved in malignant cell transformation were associated with cell adhesion molecules, extracellular matrix receptor interaction, and proteoglycans in cancer, among others, which are closely related to the occurrence and development of carcinogenesis. Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) assay showed that five screened miRNAs were up-regulated in five lung cancer tissue samples. In conclusion, the results indicated that hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257 may be potential early markers of the malignant transformation of bronchial epithelial cells induced by alpha-particle irradiation.

摘要

通过对地下矿工的流行病学研究,氡的致癌性已得到令人信服的证明。氡暴露导致肺癌的风险源于这种气体的持续放射性衰变以及随后高能α衰变粒子的发射。支气管上皮细胞是氡暴露的主要靶标。然而,在氡暴露较高职业人群的体检中,缺乏由氡引起的肺癌的早期预警指标。为了评估基于分子的标志物方法在早期检测氡诱发的人类肺癌方面的潜力,构建了由α粒子照射诱导的人支气管上皮细胞损伤模型。Transwell迁移试验、Transwell侵袭试验以及上皮-间质转化相关蛋白的表达结果表明,α照射可触发恶性细胞转化。在细胞模型中使用miRNA芯片筛选出潜在的微小RNA(miRNA)(hsa-miR-3907、hsa-miR-6732-3p、hsa-miR-4788、hsa-miR-5001-5p和hsa-miR-4257)。使用DIANA-miRPath v3.0对筛选出的miRNA进行通路分析表明,参与恶性细胞转化的miRNA与细胞粘附分子、细胞外基质受体相互作用以及癌症中的蛋白聚糖等有关,这些都与致癌作用的发生和发展密切相关。逆转录定量实时PCR(RT-qPCR)分析表明,在五个肺癌组织样本中,筛选出的五个miRNA均上调。总之,结果表明hsa-miR-3907、hsa-miR-6732-3p、hsa-miR-4788、hsa-miR-5001-5p和hsa-miR-4257可能是α粒子照射诱导支气管上皮细胞恶性转化的潜在早期标志物。

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