Wan Dong, He Lingnan, Guo Cheng, Zhong Zishao, Yan Xiaohan, Cao Jia, Xu Qinwei, Zhang Haibin, Duan Bensong
Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Front Genet. 2023 Jun 20;14:1140218. doi: 10.3389/fgene.2023.1140218. eCollection 2023.
N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD. The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry. In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells. A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.
N6-甲基腺苷(m6A)修饰是一种常见的RNA表观遗传甲基化修饰,通过调节长链非编码RNA(lncRNA)在胃癌的发生和发展中起重要作用。本研究旨在探讨m6A相关lncRNA在胃腺癌(STAD)中的潜在预后特征。通过生物信息学和机器学习方法,在TCGA数据库中鉴定出对胃癌预后影响最显著的m6A相关lncRNA。采用最小绝对收缩和选择算子(LASSO)算法的Cox回归分析构建m6A相关lncRNA预后模型(m6A-LPS)和列线图。还研究了m6A相关lncRNA的功能富集分析。利用miRTarBase、miRDB和TargetScan数据库,通过生物信息学方法建立了竞争性内源性RNA(ceRNA)的预后相关网络。通过qRT-PCR和流式细胞术实验验证了AL391152.1表达与细胞周期的相关性。总共在GC样本中鉴定出697个lncRNA为m6A相关lncRNA。生存分析表明,18个lncRNA具有预后价值。通过Lasso Cox回归建立了一个包含11个lncRNA的风险模型,可预测GC患者的预后。Cox回归分析和ROC曲线表明,该lncRNA预测模型是生存率的独立危险因素。功能富集分析和ceRNA网络显示,列线图与细胞周期显著相关。qRT-PCR和流式细胞术显示,GC中m6A相关lncRNA AL391152.1的下调可降低SGC7901细胞中细胞周期蛋白的表达。本研究建立了一种m6A相关lncRNA预后模型,可用于预测胃癌的预后和细胞周期。