Širvinskas Dovydas, Steponaitis Giedrius, Stakaitis Rytis, Tamašauskas Arimantas, Vaitkienė Paulina, Skiriutė Daina
Laboratory of Molecular Neurobiology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Laboratory of Molecular Neurooncology, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Front Mol Biosci. 2023 Mar 6;10:1101953. doi: 10.3389/fmolb.2023.1101953. eCollection 2023.
Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked effect on the survival of glioma patients. We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for and genes. These data were validated using the TCGA and GTEx gene expression databases. The gene expression level of ncNAT lncRNA in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA /lncRNA gene expression ratio compared to high ratio showing a link between lncRNA and glioma patient survival prognosis. Here we show that elevated levels of lncRNA (i.e., low ratio of mRNA A/lncRNA ) is associated with poor prognosis for glioma patients
天然非编码反义转录本（ncNATs）是从单独的蛋白质编码基因或非编码基因的相反链转录而来的长链非编码RNA（lncRNA）。因此，ncNATs可以通过稳定mRNA、吸收抑制性微小RNA（miRNA）以及保护mRNA不被降解来提高重叠mRNA（以及编码的蛋白质）水平，或者相反地，通过引导mRNA降解或抑制蛋白质翻译来降低mRNA（或蛋白质）水平。最近，越来越多的ncNATs被证明在癌细胞中表达失调，然而，ncNATs对癌症进展的实际影响在很大程度上仍然未知。因此，我们研究了天然反义lncRNA（胆固醇诱导的代谢调节RNA）及其正义链蛋白质编码基因（干扰素诱导蛋白激酶EIF2AK2的蛋白质激活剂）在胶质瘤中的基因表达水平。接下来，我们检查了其对胶质瘤患者生存的影响。我们对26例胶质瘤患者的术后肿瘤样本和正常脑组织进行了RNA测序。提取了TPM值中 和 基因的基因表达数据。这些数据使用TCGA和GTEx基因表达数据库进行了验证。与健康脑组织相比，胶质瘤组织中ncNAT lncRNA的基因表达水平显著更高，而其正义链对应蛋白质编码mRNA在胶质瘤和健康样本之间的表达没有差异。生存分析显示，mRNA/lncRNA基因表达比值低的患者生存率低于比值高的患者，表明lncRNA与胶质瘤患者生存预后之间存在联系。在这里，我们表明lncRNA水平升高（即mRNA A/lncRNA比值低）与胶质瘤患者预后不良相关
