Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Orthopedic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
DNA Cell Biol. 2020 Jul;39(7):1328-1346. doi: 10.1089/dna.2020.5590. Epub 2020 May 22.
Cervical cancer (CC) is the fourth commonest cancer in women worldwide. Increasing evidence proves that microRNA (miRNA)-messenger RNA (mRNA) network is involved in CC. In this study, miRNA and mRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Differently expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were obtained by "Empirical Analysis of Digital Gene Expression Data in R (EdgeR)" package. Then, functional analyses were conducted. With Cytoscape software, a protein-protein interaction (PPI) network was established to identify hub genes that were used for building an miRNA-hub gene network. Next, a prognostic signature based on hub genes was constructed by Cox regression analysis, and its prognostic value was assessed by a nomogram. Finally, the relationship between immune cell infiltration and the three genes in the prognostic model was investigated by using the CIBERSORT algorithm. We screened out 5096 DE-mRNAs and 114 DE-miRNAs between healthy cervical and CC tissues. Then, 102 target DE-mRNAs of upregulated DE-miRNAs and 150 target DE-mRNAs of downregulated DE-miRNAs were obtained. PPI network demonstrated 20 hub nodes with higher connectivity. DE-mRNAs were mostly enriched in pathways in cancer, cell cycle, and proteoglycans in cancer. The miRNA-hub gene network showed that most hub genes could be potentially modulated by miR-200c-3p, miR-23b-3p, and miR-106b-5p. Quantitative real-time PCR proved that 10 miRNAs were downregulated and 6 mRNAs were upregulated markedly in CC tissues. Furthermore, a prognostic signature was established based on enhancer of zeste homolog 2 (), Fms-related tyrosine kinase 1 (), and glyceraldehyde 3-phosphate dehydrogenase (). The area under the curve value of the 5-year receiver operating characteristic curve was 0.609. The three genes were also found to be related to the infiltration of six types of immune cells, including dendritic cells, macrophages M0 and M1, mast cells, and monocytes. In conclusion, the development of CC is regulated by the miRNA-mRNA network we proposed in this study.
宫颈癌（CC）是全球女性中第四常见的癌症。越来越多的证据证明，微小 RNA（miRNA）-信使 RNA（mRNA）网络参与了 CC 的发生。在本研究中，我们从癌症基因组图谱（TCGA）数据库中下载了 miRNA 和 mRNA 表达谱。通过“R 语言数字基因表达数据的经验分析（EdgeR）”软件包获得差异表达的 miRNA（DE-miRNA）和 mRNA（DE-mRNA）。然后进行功能分析。利用 Cytoscape 软件构建蛋白质-蛋白质相互作用（PPI）网络，识别枢纽基因，构建 miRNA-枢纽基因网络。接下来，通过 Cox 回归分析构建基于枢纽基因的预后标志物，并通过列线图评估其预后价值。最后，利用 CIBERSORT 算法研究免疫细胞浸润与预后模型中三个基因的关系。我们筛选出健康宫颈组织和 CC 组织之间的 5096 个 DE-mRNA 和 114 个 DE-miRNA。然后，获得上调的 DE-miRNA 的 102 个靶标 DE-mRNA 和下调的 DE-miRNA 的 150 个靶标 DE-mRNA。PPI 网络显示 20 个具有较高连接性的枢纽节点。DE-mRNA 主要富集在癌症、细胞周期和癌症中的蛋白聚糖途径中。miRNA-枢纽基因网络表明，大多数枢纽基因可能受 miR-200c-3p、miR-23b-3p 和 miR-106b-5p 的调控。实时定量 PCR 证明 10 个 miRNA 在 CC 组织中下调，6 个 mRNA 显著上调。此外，基于增强子结合蛋白 2（）、Fms 相关酪氨酸激酶 1（）和甘油醛 3-磷酸脱氢酶（）建立了预后标志物。5 年受试者工作特征曲线下面积为 0.609。这三个基因也与六种免疫细胞的浸润有关，包括树突状细胞、M0 和 M1 巨噬细胞、肥大细胞和单核细胞。总之，本研究提出的 miRNA-mRNA 网络调控了 CC 的发生发展。
