Department of Gastroenterology, Ruijin Hospital, Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Department of Gastroenterology, Dapuqiao Community Health Service Center, Shanghai 200333, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2209-2218. doi: 10.3892/mmr.2019.10478. Epub 2019 Jul 9.
Long non‑coding RNAs (lncRNAs) play critical roles in the development and progression of cancers. The present study aimed to identify novel lncRNAs and associated microRNAs (miRNAs or miRs) and mRNAs in gastric cancer. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) of 6 paired gastric cancer and normal tissues were identified using microarray. The DEmiRNAs between gastric cancer and the normal control tissues were identified using miRNA‑seq data from Cancer Genome Atlas. Common DElncRNAs from the Cancer RNA‑Seq Nexus database and circlncRNAnet database were analyzed. A DElncRNAs‑DEmiRNAs‑DEmRNAs network was constructed by target prediction. Functional enrichment analysis was employed to predict the function of DEmRNAs in the network. The correlation between the expression of DElncRNAS and DEmRNAs in the network was analyzed. The expression levels of several genes were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A total of 1,297 DElncRNAs, 2,037 DEmRNAs and 171 DEmiRNAs were identified. Among the 4 lncRNAs common to the 3 datasets, prostate androgen‑regulated transcript 1 (PART1) was selected for further analysis. The analysis identified 5 DEmiRNAs and 13 DEmRNAs in the PART1‑mediated ceRNA network. The DEmRNAs in the ceRNA network were markedly enriched in cancer‑related biological processes (response to hypoxia, positive regulation of angiogenesis and positive regulation of endothelial cell proliferation) and pathways (cGMP‑PKG signaling pathway, cAMP signaling pathway and proteoglycans in cancer). Out of the 13 DEmRNAs, 11 were positively associated with PART1. The downregulation of PART1, myosin light chain 9 (MYL9), potassium calcium‑activated channel subfamily M alpha 1 (KCNMA1), cholinergic receptor muscarinic 1 (CHRM1), solute carrier family 25 member 4 (SLC25A4) and ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) expression levels in gastric cancer was validated by RT‑qPCR. On the whole, the current study identified a novel lncRNA and associated miRNAs and mRNAs that are involved in the pathogenesis of gastric cancer that may serve as potential therapeutic targets for the treatment of gastric cancer.
长链非编码 RNA（lncRNA）在癌症的发生和发展中发挥着关键作用。本研究旨在鉴定胃癌中新型的 lncRNA 及其相关的 microRNA（miRNA 或 miR）和信使 RNA（mRNA）。采用微阵列技术鉴定了 6 对胃癌和正常组织中差异表达的 lncRNA（DElncRNA）和差异表达的 mRNA（DEmRNA）。采用癌症基因组图谱（Cancer Genome Atlas）中的 miRNA-seq 数据鉴定了胃癌与正常对照组织之间的差异表达 miRNA（DEmiRNA）。对来自癌症 RNA-seq Nexus 数据库和 circlncRNAnet 数据库的共同 DElncRNA 进行分析。通过靶标预测构建 DElncRNAs-DEmiRNAs-DEmRNA 网络。采用功能富集分析预测网络中 DEmRNA 的功能。分析网络中 DElncRNA 和 DEmRNA 之间的表达相关性。通过反转录-定量聚合酶链反应（RT-qPCR）验证几个基因的表达水平。鉴定到 1297 个 DElncRNA、2037 个 DEmRNA 和 171 个 DEmRNA。在 3 个数据集共有的 4 个 lncRNA 中，选择前列腺雄激素调节转录物 1（PART1）进行进一步分析。分析鉴定了 PART1 介导的 ceRNA 网络中的 5 个 DEmRNA 和 13 个 DEmRNA。ceRNA 网络中的 DEmRNA 显著富集在癌症相关的生物学过程（缺氧反应、血管生成的正调节和内皮细胞增殖的正调节）和通路（cGMP-PKG 信号通路、cAMP 信号通路和癌症中的糖蛋白）中。在 13 个 DEmRNA 中，有 11 个与 PART1 呈正相关。通过 RT-qPCR 验证了 PART1、肌球蛋白轻链 9（MYL9）、钾钙激活通道亚家族 M 阿尔法 1（KCNMA1）、毒蕈碱型乙酰胆碱受体 M1（CHRM1）、溶质载体家族 25 成员 4（SLC25A4）和三磷酸腺苷酶 Na+/K+转运亚基 alpha 2（ATP1A2）在胃癌中的下调表达。总体而言，本研究鉴定了一种新型的 lncRNA 及其相关的 miRNA 和 mRNA，它们参与了胃癌的发病机制，可能成为治疗胃癌的潜在治疗靶点。
