长链非编码 RNA 失调是非小细胞肺癌发病机制中的常见事件。
Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis.
机构信息
Roy Castle Lung Cancer Programme, Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology (IRDB), Imperial College London, London, UK.
出版信息
Br J Cancer. 2020 Mar;122(7):1050-1058. doi: 10.1038/s41416-020-0742-9. Epub 2020 Feb 5.
BACKGROUND
Long non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease. Despite the plethora of publications of lncRNAs in human cancer, the landscape is still unclear.
METHODS
Microarray analysis in 44 NSCLC paired specimens was followed by qPCR-based validation in 29 (technical) and 38 (independent) tissue pairs. Cross-validation of the selected targets was achieved in 850 NSCLC tumours from TCGA datasets.
RESULTS
Twelve targets were successfully validated by qPCR (upregulated: FEZF1-AS1, LINC01214, LINC00673, PCAT6, NUTM2A-AS1, LINC01929; downregulated: PCAT19, FENDRR, SVIL-AS1, LANCL1-AS1, ADAMTS9-AS2 and LINC00968). All of them were successfully cross validated in the TCGA datasets. Abnormal DNA methylation was observed in the promoters of FENDRR, FEZF1-AS1 and SVIL-AS1. FEZF1-AS1 and LINC01929 were associated with survival in the TCGA set.
CONCLUSIONS
Our study provides through multiple levels of internal and external validation, a comprehensive list of dysregulated lncRNAs in NSCLC. We therefore envisage this dataset to serve as an important source for the lung cancer research community assisting future investigations on the involvement of lncRNAs in the pathogenesis of the disease and providing novel biomarkers for diagnosis, prognosis and therapeutic stratification.
背景
长非编码 RNA 在正常生理和疾病中构成了表观遗传调控的重要层次。尽管人类癌症中 lncRNA 的大量出版物很多，但情况仍不清楚。
方法
对 44 对 NSCLC 配对标本进行微阵列分析，然后在 29 对（技术）和 38 对（独立）组织对中进行基于 qPCR 的验证。在 TCGA 数据集的 850 个 NSCLC 肿瘤中实现了所选靶标的交叉验证。
结果
通过 qPCR 成功验证了 12 个靶标（上调：FEZF1-AS1、LINC01214、LINC00673、PCAT6、NUTM2A-AS1、LINC01929；下调：PCAT19、FENDRR、SVIL-AS1、LANCL1-AS1、ADAMTS9-AS2 和 LINC00968）。所有这些都在 TCGA 数据集中成功交叉验证。在 FENDRR、FEZF1-AS1 和 SVIL-AS1 的启动子中观察到异常 DNA 甲基化。FEZF1-AS1 和 LINC01929 与 TCGA 集中的生存相关。
结论
我们的研究通过内部和外部的多重验证，提供了 NSCLC 中失调的 lncRNA 的综合列表。因此，我们预计该数据集将成为肺癌研究界的重要资源，协助未来对 lncRNA 参与疾病发病机制的研究，并为诊断、预后和治疗分层提供新的生物标志物。
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