Bai Ming, Sun Chen
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Cell Dev Biol. 2022 May 3;10:885568. doi: 10.3389/fcell.2022.885568. eCollection 2022.
Epigenetic RNA modification regulates gene expression post-transcriptionally. The aim of this study was to construct a prognostic risk model for lung adenocarcinoma (LUAD) using long non-coding RNAs (lncRNAs) related to m5C RNA methylation. The lncRNAs regulated by m5C methyltransferase were identified in TCGA-LUAD dataset using Pearson correlation analysis (coefficient > 0.4), and clustered using non-negative matrix decomposition. The co-expressing gene modules were identified by WGCNA and functionally annotated. The prognostically relevant lncRNAs were screened by LASSO regression and a risk model was constructed. LINC00628 was silenced in the NCI-H460 and NCI-H1299 cell lines using siRNA constructs, and migration and invasion were assessed by the Transwell and wound healing assays respectively. We identified 185 m5C methyltransferase-related lncRNAs in LUAD, of which 16 were significantly associated with overall survival. The lncRNAs were grouped into two clusters on the basis of m5C pattern, and were associated with significant differences in overall and disease-free survival. GSVA revealed a close relationship among m5C score, ribosomes, endolysosomes and lymphocyte migration. Using LASSO regression, we constructed a prognostic signature consisting of LINC00628, LINC02147, and MIR34AHG. The m5C-lncRNA signature score was closely related to overall survival, and the accuracy of the predictive model was verified by the receiver operating characteristic curve and decision curve analysis. Knocking down LINC00628 in NCI-H460 and NCI-H1299 cells significantly reduced their migration and invasion compared to that of control cells. We constructed a prognostic risk model of LUAD using three lncRNAs regulated by m5C methyltransferase, which has potential clinical value.
表观遗传RNA修饰在转录后水平调节基因表达。本研究的目的是利用与m5C RNA甲基化相关的长链非编码RNA（lncRNA）构建肺腺癌（LUAD）的预后风险模型。使用Pearson相关分析（系数>0.4）在TCGA-LUAD数据集中鉴定受m5C甲基转移酶调控的lncRNA，并使用非负矩阵分解进行聚类。通过WGCNA鉴定共表达基因模块并进行功能注释。通过LASSO回归筛选与预后相关的lncRNA并构建风险模型。使用siRNA构建体在NCI-H460和NCI-H1299细胞系中沉默LINC00628，并分别通过Transwell和伤口愈合试验评估迁移和侵袭能力。我们在LUAD中鉴定出185个与m5C甲基转移酶相关的lncRNA，其中16个与总生存期显著相关。基于m5C模式将lncRNA分为两个簇，并且与总生存期和无病生存期的显著差异相关。GSVA揭示了m5C评分、核糖体、内溶酶体和淋巴细胞迁移之间的密切关系。使用LASSO回归，我们构建了一个由LINC00628、LINC02147和MIR34AHG组成的预后特征。m5C-lncRNA特征评分与总生存期密切相关，并且通过受试者工作特征曲线和决策曲线分析验证了预测模型的准确性。与对照细胞相比，在NCI-H460和NCI-H1299细胞中敲低LINC00628显著降低了它们的迁移和侵袭能力。我们使用受m5C甲基转移酶调控的三个lncRNA构建了LUAD的预后风险模型，该模型具有潜在的临床价值。
