Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Hypertension Research Center, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
J Cell Biochem. 2019 Sep;120(9):15648-15660. doi: 10.1002/jcb.28831. Epub 2019 May 5.
Competing endogenous RNA (ceRNA) network is dysregulated in the initiation and progression of tumors. In the present study, we explored the regulatory mechanism of ceRNA in endometrial carcinoma (EC) and the potential key molecules with potential value in the diagnosis, treatment, and prognosis of EC. The long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles (552 EC tissues and 35 nontumor tissues) and microRNAs (miRNAs) expression profiles (546 EC tissues and 33 nontumor tissues) were downloaded from The Cancer Genome Atlas database to identify differentially expressed RNAs (DERNAs) in EC. An integrated bioinformatics analysis was used to construct an EC-specific ceRNA network and select key molecules. As a result, 96 differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 77 differentially expressed mRNAs (DEmRNAs) were identified. An EC-specific ceRNA network was built based on nine DElncRNAs significantly associated with overall survival. CCNB1 was found as a key gene in EC through the weighted gene coexpression network analysis and protein-protein interaction network analysis. Our ceRNA network showed C2orf48 and LINC00483 might upregulate CCNB1 via competing with miR-183. In addition, we found a subnetwork which contained survival-associated DERNAs (AC110491.1, LINC00483-miR-192-GRHL1). The results of reverse transcription quantitative polymerase chain reaction supported the relative expressions of C2orf48, LINC00483 were upregulated and that of AC110491.1 was downregulated in EC. We further found C2orf48 was upregulated in serous EC, endometrioid EC, and mixed serous and endometrioid EC. LINC00483 was upregulated in mixed serous and endometrioid EC compared with that in the normal tissues according to UALCAN database. In addition, candidate small molecular drugs were screened out by ConnectivityMap based on the 77 DEmRNAs in the ceRNA network. Eventually, C2orf48, LINC00483, and AC110491.1 were identified as three key lncRNAs in EC.
竞争内源性 RNA(ceRNA)网络在肿瘤的发生和发展中失调。在本研究中,我们探讨了 ceRNA 在子宫内膜癌(EC)中的调控机制,以及在 EC 的诊断、治疗和预后中有潜在价值的潜在关键分子。从癌症基因组图谱数据库中下载了长链非编码 RNA(lncRNA)和信使 RNA(mRNA)表达谱(552 例 EC 组织和 35 例非肿瘤组织)和 microRNA(miRNA)表达谱(546 例 EC 组织和 33 例非肿瘤组织),以鉴定 EC 中的差异表达 RNA(DERNAs)。采用整合的生物信息学分析构建 EC 特异性 ceRNA 网络并筛选关键分子。结果显示,鉴定出 96 个差异表达的 lncRNA(DElncRNA)、29 个差异表达的 miRNA(DEmiRNA)和 77 个差异表达的 mRNA(DEmRNA)。基于与总生存期显著相关的 9 个 DElncRNA 构建了 EC 特异性 ceRNA 网络。通过加权基因共表达网络分析和蛋白质-蛋白质相互作用网络分析发现,CCNB1 是 EC 中的关键基因。我们的 ceRNA 网络显示,C2orf48 和 LINC00483 可能通过与 miR-183 竞争而上调 CCNB1。此外,我们发现了一个包含与生存相关的 DERNAs(AC110491.1、LINC00483-miR-192-GRHL1)的子网络。逆转录定量聚合酶链反应的结果支持了在 EC 中 C2orf48、LINC00483 的相对表达上调和 AC110491.1 的相对表达下调。我们进一步发现,在 UALCAN 数据库中,C2orf48 在浆液性 EC、子宫内膜样 EC 和混合浆液性和子宫内膜样 EC 中上调,LINC00483 在混合浆液性和子宫内膜样 EC 中与正常组织相比上调。此外,根据 ConnectivityMap 筛选出 ceRNA 网络中 77 个 DEmRNA 的候选小分子药物。最终,C2orf48、LINC00483 和 AC110491.1 被确定为 EC 中的三个关键 lncRNA。