Construction of novel mRNA-miRNA-lncRNA regulatory networks associated with prognosis of ovarian cancer.
Construction of novel mRNA-miRNA-lncRNA regulatory networks associated with prognosis of ovarian cancer.
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与卵巢癌预后相关的新型mRNA-miRNA-lncRNA调控网络的构建
DOI：
10.7150/jca.49557
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发表时间：
2020
影响因子：
3.9
通讯作者：
Lin B
中科院分区：
文献类型：
--
作者：
Gao L;Li X;Nie X;Guo Q;Liu Q;Qi Y;Liu J;Lin B
背景：卵巢癌（OC）是女性生殖系统中最致命的恶性肿瘤。越来越多的证据表明，竞争性内源RNA（ceRNA）网络在肿瘤的发生和进展中发挥着至关重要的作用。因此，我们的目的是探索和鉴定与 OC 预后相关的新型 mRNA-miRNA-lncRNA ceRNA 网络。方法：从基因表达综合（GEO）数据库中收集四个表达谱数据集（GSE5438、GSE40595、GSE38666和GSE26712）的差异表达基因（DEG）并使用NetworkAnalyst进行分析。 DEG 的交集进一步用于基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 通路分析。蛋白质-蛋白质相互作用（PPI）网络和 DEG 的中心基因也被确定。通过各种生物信息学数据库对OC中的hub基因及其上游miRNA和lncRNA的表达水平和存活率进行分析。更重要的是，ceRNA网络是基于OC中的mRNA-miRNA-lncRNA构建的。结果：在 OC 中，从 4 个表达谱的交叉 DEG 中鉴定出总共 178 个 DEG，其中包括 38 个上调基因和 140 个下调基因。功能富集分析表明，常见的DEGs富集于调节酶抑制剂活性、糖胺聚糖和G蛋白偶联受体结合、细胞形态发生，并参与代谢过程、癌症中的蛋白聚糖等途径。选择连接度最高的前10个hub基因进行后续的表达和预后分析。考虑到 OC 中 hub 基因及其上游 miRNA 和 lncRNA 的表达水平和预后作用，2 个 mRNA（TACC3 和 CXCR4）、2 个 miRNA（hsa-miR-425-5p 和 hsa-miR-146a-5p）和 3 个 lncRNA（FUT8-AS1、LINC00665 和 LINC01535）与 OC 的不良预后显着相关。 OC。最终基于ceRNA机制在OC中构建了mRNA-miRNA-lncRNA网络（TACC3-hsa-miR-425-5p-FUT8-AS1和CXCR4-hsa-miR-146a-5p-LINC00665/LINC01535）。结论：我们成功构建了与卵巢癌预后相关的新型ceRNA网络，可能为OC的早期诊断和治疗干预提供新策略。
Background: Ovarian cancer (OC) is the most lethal malignancy in the female reproductive system. Growing evidences demonstrates that competing endogenous RNA (ceRNA) network play crucial roles in the occurrence and progression of tumors. Therefore, we aimed to explore and identify novel mRNA-miRNA-lncRNA ceRNA networks associated with prognosis of OC. Methods: The differentially expressed gene (DEGs) of four expression profiles datasets (GSE5438, GSE40595, GSE38666 and GSE26712) were collected from Gene Expression Omnibus (GEO) database and analyzed with NetworkAnalyst. Intersection of DEGs were further employed for Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. Protein-protein interaction (PPI) network and hub genes of DEGs were also identified. The expression levels and survival analysis of the hub genes in OC and their upstream miRNAs and lncRNAs were performed by various bioinformatics databases. More importantly, ceRNA networks were constructed based on mRNA-miRNA-lncRNA in OC. Results: A total of 178 DEGs including 38 upregulated and 140 downregulated genes from intersected DEGs of four expression profiles were identified in OC. Functional enrichment analysis suggested that the commonly DEGs were enriched in regulating enzyme inhibitor activity, glycosaminoglycan and G protein-coupled receptor binding, cell morphogenesis, and involved in pathways including metabolic process, proteoglycans in cancer. Top 10 hub genes with higher connectivity degree were selected for subsequent expression and prognosis analysis. After take expression levels and prognostic roles of hub genes and their upstream miRNAs and lncRNAs in OC into consideration, 2 mRNAs (TACC3 and CXCR4), 2 miRNAs (hsa-miR-425-5p and hsa-miR-146a-5p) and 3 lncRNAs (FUT8-AS1, LINC00665 and LINC01535) were significantly associated with the poor prognosis of OC. The mRNA-miRNA-lncRNA networks (TACC3-hsa-miR-425-5p-FUT8-AS1 and CXCR4-hsa-miR-146a-5p-LINC00665/LINC01535) were eventually constructed in OC based on ceRNA mechanism. Conclusion: We successfully constructed novel ceRNA network associated with the prognosis of ovarian cancer, which may provide a new strategy for early diagnosis and therapeutic intervention of OC.
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影响因子：
9.7
作者：
Reicher, Andreas;Fosselteder, Johannes;Pichler, Martin
通讯作者：
Pichler, Martin
影响因子：
9
作者：
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通讯作者：
Huang WR
影响因子：
14.9
作者：
Chang, Le;Zhou, Guangyan;Xia, Jianguo
通讯作者：
Xia, Jianguo
影响因子：
5.6
作者：
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通讯作者：
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影响因子：
13.5
作者：
Ding, Jie;Zhao, Jingjing;He, Xianghuo
通讯作者：
He, Xianghuo