Tang Siqi, Liao Keyong, Shi Yongpeng, Tang Tingting, Cui Beibei, Huang Zunnan
Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University Dongguan 523808, Guangdong, China.
The Second School of Clinical Medicine, Guangdong Medical University Dongguan 523808, Guangdong, China.
Am J Cancer Res. 2022 May 15;12(5):2397-2418. eCollection 2022.
Gastric cancer (GC), the fifth most common malignancy worldwide, has an extremely poor prognosis at the advanced stage or the early stage if inadequately treated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs all function as competing endogenous RNAs (ceRNAs) that target and regulate each other. Changes in their expression and their regulatory bioprocesses play important roles in GC. However, the roles of key RNAs and their regulatory networks remain unclear. In this study, RNA profiles were extracted from The Cancer Genome Atlas database, and R language was used to discover the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in GC. Then, the DERNAs were paired by miRcode, miRDB, TargetScan and DIANA, and the ceRNA network was further constructed and visualized using Cytoscape. Moreover, a functional enrichment analysis was performed using Metascape. Afterward, the "survival" package was employed to identify candidate prognostic targets (DERNA-os) in the ceRNA network. Ultimately, the ceRNA network was analyzed to identify crucial lncRNA/miRNA/mRNA axes. Based on 374 gastric adenocarcinoma and gastric adenoma samples, 283 DEceRNAs (69 lncRNAs, 10 miRNAs, and 204 mRNAs) were identified. The 204 mRNAs were significantly enriched in some interesting functional clusters, such as the trans-synaptic signaling cluster and the protein digestion and absorption cluster. The ceRNA network consisted of 43 ceRNAs (13 lncRNAs, 2 miRNAs, and 28 mRNAs) that were related to prognosis. Among them, 2 lncRNAs (LNC00469 and AC010145.1) and 1 mRNA (PRRT4) were potential new biomarkers. In addition, according to the lncRNA/miRNA/mRNA regulatory relationships among the 43 ceRNAs, we identified four axes that might play important roles in the progression of GC and investigated the potential mechanism of the most promising axis (POU6F2-AS2/hsa-mir-137/OPCML) in promoting the proliferation and invasiveness of GC.
胃癌（GC）是全球第五大常见恶性肿瘤，若治疗不当，无论处于晚期还是早期，其预后都极差。长链非编码RNA（lncRNA）、微小RNA（miRNA）和信使RNA（mRNA）均作为竞争性内源RNA（ceRNA）发挥作用，它们相互靶向并调节。其表达变化及其调控生物过程在胃癌中起重要作用。然而，关键RNA及其调控网络的作用仍不清楚。在本研究中，从癌症基因组图谱数据库中提取RNA谱，并使用R语言发现胃癌中差异表达的（DE）lncRNA、miRNA和mRNA。然后，通过miRcode、miRDB、TargetScan和DIANA对差异表达RNA（DERNA）进行配对，并使用Cytoscape进一步构建和可视化ceRNA网络。此外，使用Metascape进行功能富集分析。之后，使用“生存”包在ceRNA网络中识别候选预后靶点（DERNA-os）。最终，对ceRNA网络进行分析以识别关键的lncRNA/miRNA/mRNA轴。基于374例胃腺癌和胃腺瘤样本，鉴定出283个DEceRNA（69个lncRNA、10个miRNA和204个mRNA）。这204个mRNA在一些有趣的功能簇中显著富集，如跨突触信号簇和蛋白质消化与吸收簇。ceRNA网络由43个与预后相关的ceRNA（13个lncRNA、2个miRNA和28个mRNA）组成。其中，2个lncRNA（LNC00469和AC010145.1）和1个mRNA（PRRT4）是潜在的新生物标志物。此外，根据43个ceRNA之间的lncRNA/miRNA/mRNA调控关系，我们确定了四个可能在胃癌进展中起重要作用的轴，并研究了最有前景的轴（POU6F2-AS2/hsa-mir-137/OPCML）促进胃癌增殖和侵袭的潜在机制。
