Wang Jing, Li Jie
Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Arch Med Sci. 2021 Feb 9;20(2):539-556. doi: 10.5114/aoms/131198. eCollection 2024.
Long non-coding RNAs (lncRNAs) functioning as competing endogenous RNAs (ceRNAs) play critical roles in tumour progression. However, prognosis-related ceRNA networks in lung adenocarcinoma (LUAD) have not been well characterised.
LUAD datasets were downloaded from the TCGA database, and the patients were divided into metastasis and non-metastasis groups. The differential expression of lncRNAs (DELs), miRNAs (DEMs), and mRNAs (DEGs) was analysed using the Limma package. Next, interactions between miRNA, lncRNA, and mRNA were predicted by miRcode, miRTar-Base, miRDB, and TargetScan. The ceRNA network was constructed based on these interactions using Cytoscape software. DEG enrichment analysis was performed by GO and KEGG. After the prognosis analysis, we further screened molecules and constructed the prognosis-related ceRNA network. Moreover, the interactions between lncRNA, miRNA, and mRNA were validated by biological experiments.
854 DELs, 150 DEMs, and 2211 DEGs between metastasis and non-metastasis LUAD patients were identified. Functional enrichment analysis suggested that DEGs were closely related to key biological processes involved in LUAD progression. The prognosis-related ceRNA network included 1 miRNA, 2 lncRNAs, and 4 mRNAs. In this network, MIR155HG and ADAMTS9-AS2 can function as ceRNAs of miR-212 to regulate EPM2AIP1, LAX1, PRICKLE2, and CD226. Moreover, our study confirmed that MIR155HG inhibited the proliferation, migration, and invasion of LUAD cells by sponging miR-212-3p to regulate CD226.
This ceRNA network contributes to understanding the pathogenesis of LUAD. Furthermore, the molecules in the network are valuable predictive factors for LUAD prognosis as well as potential therapeutic biomarkers.
作为竞争性内源RNA(ceRNA)发挥作用的长链非编码RNA(lncRNA)在肿瘤进展中起关键作用。然而,肺腺癌(LUAD)中与预后相关的ceRNA网络尚未得到充分表征。
从TCGA数据库下载LUAD数据集,并将患者分为转移组和非转移组。使用Limma软件包分析lncRNA(DEL)、miRNA(DEM)和mRNA(DEG)的差异表达。接下来,通过miRcode、miRTar-Base、miRDB和TargetScan预测miRNA、lncRNA和mRNA之间的相互作用。使用Cytoscape软件基于这些相互作用构建ceRNA网络。通过GO和KEGG进行DEG富集分析。经过预后分析后,我们进一步筛选分子并构建与预后相关的ceRNA网络。此外,通过生物学实验验证了lncRNA、miRNA和mRNA之间的相互作用。
在转移和非转移LUAD患者之间鉴定出854个DEL、150个DEM和2211个DEG。功能富集分析表明,DEG与LUAD进展中涉及的关键生物学过程密切相关。与预后相关的ceRNA网络包括1个miRNA、2个lncRNA和4个mRNA。在这个网络中,MIR155HG和ADAMTS9-AS2可以作为miR-212的ceRNA来调节EPM2AIP1、LAX1、PRICKLE2和CD226。此外,我们的研究证实,MIR155HG通过海绵吸附miR-212-3p来调节CD226,从而抑制LUAD细胞的增殖、迁移和侵袭。
这个ceRNA网络有助于理解LUAD的发病机制。此外,网络中的分子是LUAD预后的有价值预测因素以及潜在的治疗生物标志物。