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 (EZH2), Fms-related tyrosine kinase 1 (FLT1), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). 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.

中文翻译：

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microRNA-Messenger RNA调控网络及其在宫颈癌中的预后价值。

宫颈癌（CC）是全球女性中第四大最常见的癌症。越来越多的证据证明，microRNA（miRNA）-信使RNA（mRNA）网络参与了CC。在这项研究中，miRNA和mRNA表达谱从癌症基因组图谱（TCGA）数据库下载。通过“ R中的数字基因表达数据的经验分析（EdgeR）”软件包获得了差异表达的miRNA（DE-miRNA）和mRNA（DE-mRNA）。然后，进行功能分析。借助Cytoscape软件，建立了蛋白质-蛋白质相互作用（PPI）网络，以识别用于构建miRNA-hub基因网络的集线器基因。接下来，通过Cox回归分析构建基于中心基因的预后签名，并通过诺模图评估其预后价值。最后，用CIBERSORT算法研究了免疫细胞浸润与三个基因在预后模型中的关系。我们筛选出健康的宫颈和CC组织之间的5096个DE-mRNA和114个DE-miRNA。然后，获得了上调的DE-miRNA的102个靶DE-mRNA和下调的DE-miRNA的150个靶DE-mRNA。PPI网络展示了20个具有更高连接性的集线器节点。DE-mRNA在癌症，细胞周期和蛋白聚糖中的途径中最丰富。miRNA-hub基因网络显示，大多数集线器基因都可能受到miR-200c-3p，miR-23b-3p和miR-106b-5p的调节。实时定量PCR证实CC组织中有10个miRNA被下调，而6个mRNA被显着上调。此外，基于zeste同源2的增强子建立了预后标记（EZH2），Fms相关酪氨酸激酶1（FLT1）和3-磷酸甘油醛脱氢酶（GAPDH）。五年接收器工作特性曲线的曲线值下的面积为0.609。还发现这三个基因与六种类型免疫细胞的浸润有关，包括树突状细胞，巨噬细胞M0和M1，肥大细胞和单核细胞。总之，CC的发育受我们在这项研究中提出的miRNA-mRNA网络调控。