Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, China.
Int J Med Sci. 2021 Jan 1;18(2):419-431. doi: 10.7150/ijms.49730. eCollection 2021.
In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network. GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2. 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells. LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.
近年来，LncRNA 作为竞争性内源 RNA (ceRNA) 的成员，在肺癌耐药中发挥重要作用。本研究旨在通过综合 ceRNA 网络鉴定顺铂耐药肺癌细胞的潜在生物标志物。GSE6410（GPL-201）分析了 A549 NSCLC 细胞顺铂耐药相关的基因表达变化。GSE43249（GPL-14613）包括源自顺铂耐药 A549 肺细胞的非编码 RNA 表达谱。在线分析工具 GEO2R 分析了差异表达的 mRNAs 和 miRNAs（DEmRNAs 和 DEmiRNAs）。为了探讨差异表达 mRNAs 的功能富集意义，我们使用了 GO（基因本体论）和 KEGG（京都基因与基因组百科全书）通路分析。通过 miRDB、Targetscan、Starbase 和 miRWalk，我们找到了靶向 miRNAs。Kaplan-Meier 曲线法用于显示靶向 RNA（）的临床生存分析。Starbase 数据库预测了潜在的 lncRNA 介导的靶向 miRNAs。最后，通过 cytoscape3.7.2 构建了 lncRNA、miRNA、mRNA 的新型 ceRNA 网络。118 个差异表达的 mRNAs 是介导 ceRNA 网络的基础。DAVID 和 Kaplan-Meier 挑选出凋亡调节因子 BAX。Venn 图显示了 8 个共同调节 BAX 的 miRNA。Starbase 预测了 lncRNA XIST 介导的 miRNAs。最后，lncRNA XIST 可能是调节肺癌细胞顺铂耐药的有用生物标志物，进一步探索了 BAX 可能影响肿瘤浸润免疫细胞。lncRNA XIST 通过 BAX 竞争性结合 miRNA 520 参与顺铂耐药的调控，参与 p53 信号通路的细胞凋亡。
