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石棉纤维暴露后间皮细胞和间皮瘤细胞系中小 RNA 和 tRNA 衍生的 ncRNA 的失调。

Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.

机构信息

Human Anatomy and Histology Unit, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.

Bioinformatics Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123, Catania, Italy.

出版信息

Sci Rep. 2022 Jun 2;12(1):9181. doi: 10.1038/s41598-022-13044-0.

DOI:10.1038/s41598-022-13044-0
PMID:35654808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9163335/
Abstract

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.

摘要

实验证据表明，氟镁闪石（FE）可引发慢性呼吸道疾病和致癌作用。暴露于 FE 纤维环境与恶性胸膜间皮瘤（MPM）有关。MPM 的早期诊断以及对暴露于 FE 纤维的患者进行全面健康监测，可能通过鉴定特定的生物标志物来解决这两个临床问题。我们报告了人类正常间皮细胞和恶性间皮瘤细胞系在暴露或不暴露于几种浓度 FE 纤维的情况下的 microRNA（miRNA）和转移 RNA 衍生的非编码 RNA（tRNA 衍生的 ncRNA）转录组。此外，还使用 NetME 工具得出了基于交互性间皮瘤的网络。在未处理条件下，肿瘤细胞中的 miRNA 和 tRNA 衍生的 ncRNA 的表达与非肿瘤样本相比存在显著差异。此外，在两种细胞系暴露于 FE 纤维后，发现了有趣且显著的变化。基于网络的途径分析显示，几种信号转导和代谢途径可能参与了 MPM 的发病机制。从 NetME 分析的论文中可以清楚地看出，许多 miRNA 可以积极或消极地影响 MPM 涉及的各种途径。这是首次在体外系统中对间皮瘤中 tRNA 衍生的 ncRNA 分子进行分析。将进一步设计研究以测试和验证它们在高危个体的液体活检中的诊断潜力。

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