Arenas Alberto M, Cuadros Marta, Andrades Alvaro, García Daniel J, Coira Isabel F, Rodríguez María Isabel, Baliñas-Gavira Carlos, Peinado Paola, Álvarez-Pérez Juan Carlos, Medina Pedro P
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. de Fuente Nueva s/n, 18071 Granada, Spain.
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18007 Granada, Spain.
Cancers (Basel). 2020 Jul 28;12(8):2080. doi: 10.3390/cancers12082080.
Long non-coding RNAs (lncRNAs) are a heterogeneous class of non-coding RNAs whose biological roles are still poorly understood. LncRNAs serve as gene expression regulators, frequently interacting with epigenetic factors to shape the outcomes of crucial biological processes, and playing roles in different pathologies including cancer. Over the last years, growing scientific evidence supports the key role of some lncRNAs in tumor development and proposes them as valuable biomarkers for the clinic. In this study, we aimed to characterize lncRNAs whose expression is altered in tumor samples from patients with lung adenocarcinoma (LUAD) compared to adjacent normal tissue samples. On an RT-qPCR survey of 90 cancer-related lncRNAs, we found one lncRNA, DLG2-AS1, which was consistently downregulated in 70 LUAD patients. To gain insight into its biological function, DLG2-AS1 was cloned and successfully re-expressed in LUAD cancer cell lines. We determined that DLG2-AS1 is not a cis-regulatory element of its overlapping gene DLG2, as their transcription levels were not correlated, nor did DLG2-AS1 restoration modify the expression of DLG2 protein. Furthermore, after generating a receiver operating curve (ROC) and calculating the area under curve (AUC), we found that DLG2-AS1 expression showed high sensitivity and specificity (AUC = 0.726) for the classification of LUAD and normal samples, determining its value as a potential lung cancer biomarker.
长链非编码RNA（lncRNAs）是一类异质性的非编码RNA，其生物学功能仍知之甚少。lncRNAs作为基因表达调节因子，经常与表观遗传因子相互作用，以塑造关键生物学过程的结果，并在包括癌症在内的不同病理过程中发挥作用。在过去几年中，越来越多的科学证据支持某些lncRNAs在肿瘤发生发展中的关键作用，并提出它们可作为临床上有价值的生物标志物。在本研究中，我们旨在鉴定与相邻正常组织样本相比，在肺腺癌（LUAD）患者肿瘤样本中表达发生改变的lncRNAs。在对90种癌症相关lncRNAs进行的RT-qPCR检测中，我们发现一种lncRNA，即DLG2-AS1，在70例LUAD患者中持续下调。为深入了解其生物学功能，我们克隆了DLG2-AS1并在LUAD癌细胞系中成功重新表达。我们确定DLG2-AS1不是其重叠基因DLG2的顺式调节元件，因为它们的转录水平不相关，DLG2-AS1的恢复也未改变DLG2蛋白的表达。此外，在生成受试者工作特征曲线（ROC）并计算曲线下面积（AUC）后，我们发现DLG2-AS1表达对LUAD和正常样本的分类具有高敏感性和特异性（AUC = 0.726），确定了其作为潜在肺癌生物标志物的价值。
