Yang Lijie, Yang Tiecheng, Wang Huaqiao, Dou Tingting, Fang Xiaochang, Shi Liwen, Li Xuanfei, Feng Maohui
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Clinical Cancer Study Center of Hubei Provence, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan, China.
Front Oncol. 2022 Apr 27;12:765163. doi: 10.3389/fonc.2022.765163. eCollection 2022.
Long non-coding RNAs (LncRNAs) act as competing endogenous RNAs (ceRNAs) in colon cancer (CC) progression, binding microRNAs (miRNAs) to regulate the expression of corresponding messenger RNAs (mRNAs). This article aims to explore the detailed molecular mechanism of ceRNA in CC. Top mad 5000 lncRNAs and top mad 5000 mRNAs were used to perform weighted gene co-expression network analysis (WGCNA), and key modules were selected. We used 405 lncRNAs in the red module and 145 mRNAs in the purple module to build the original ceRNA network by online databases. The original ceRNA network included 50 target lncRNAs, 41 target miRNAs, and 34 target mRNAs. Fifty target lncRNAs were used to establish a prognostic risk model by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. LncRNAs in the risk model were used to build the secondary ceRNA network, which contained 9 lncRNAs in the risk model, 35 miRNAs, and 29 mRNAs. Survival analyses of 29 mRNAs in the secondary ceRNA network have shown HOXA10 and NHLRC3 were identified as crucial prognostic factors. Finally, we constructed the last ceRNA network including 5 lncRNAs in the risk model, 8 miRNAs, and 2 mRNAs related to prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DNMBP-AS1 and FAM87A were down-regulated in CC cells and tissues. Function assays showed that over-expression of DNMBP-AS1 and FAM87A inhibited CC cells proliferation and migration. Mechanism study showed that DNMBP-AS1 served as miR-93-5p/17-5p sponges and relieved the suppression effect of miR-93-5p/17-5p on their target NHLRC3. Our study suggested that DNMBP-AS1 inhibited the progression of colon cancer through the miR-93-5p/17-5p/NHLRC3 axis, which could be potential therapeutic targets for CC.
长链非编码RNA（LncRNAs）在结肠癌（CC）进展中作为竞争性内源性RNA（ceRNAs）发挥作用，通过结合微小RNA（miRNAs）来调节相应信使RNA（mRNAs）的表达。本文旨在探究ceRNA在CC中的详细分子机制。使用前5000个mad lncRNAs和前5000个mad mRNAs进行加权基因共表达网络分析（WGCNA），并选择关键模块。我们利用红色模块中的405个lncRNAs和紫色模块中的145个mRNAs通过在线数据库构建原始ceRNA网络。原始ceRNA网络包括50个靶lncRNAs、41个靶miRNAs和34个靶mRNAs。通过单因素和最小绝对收缩与选择算子（LASSO）Cox回归分析，使用50个靶lncRNAs建立预后风险模型。风险模型中的lncRNAs用于构建二级ceRNA网络，该网络包含风险模型中的9个lncRNAs、35个miRNAs和29个mRNAs。对二级ceRNA网络中29个mRNAs的生存分析表明，HOXA10和NHLRC3被确定为关键预后因素。最后，我们构建了最终的ceRNA网络，包括风险模型中的5个lncRNAs、8个miRNAs和2个与预后相关的mRNAs。定量实时聚合酶链反应（qRT-PCR）结果显示，DNMBP-AS1和FAM87A在CC细胞和组织中表达下调。功能实验表明，DNMBP-AS1和FAM87A的过表达抑制CC细胞增殖和迁移。机制研究表明，DNMBP-AS1作为miR-93-5p/17-5p的海绵，减轻了miR-93-5p/17-5p对其靶标NHLRC3的抑制作用。我们的研究表明，DNMBP-AS1通过miR-93-5p/17-5p/NHLRC3轴抑制结肠癌进展，这可能是CC的潜在治疗靶点。
