This investigation aimed to explore the underlying prognosis-associated microRNA (miRNA) biomarkers in endometrial cancer. Homo sapiens miRNA data set GSE35794 and miRNA data in TGGA database were downloaded and applied to screen the differentially expressed miRNAs (DE-miRNAs) using unpaired t-test in limma package in R. Basing on Venn analysis, the overlapped DE-miRNAs were screened and their potential targets were predicted according to miRWalk followed by target functional enrichment analyses and protein–protein interaction network visualized using Cytoscape. Finally, according to the information provided by the The Cancer Genome Atlas (TCGA) database, correlations between miRNAs or targets and patient prognosis were analyzed by survival package in R. A total of 24 overlapped DE-miRNAs were identified between endometrioid endometrial cancer samples and normal samples. Then, the miRNA-target regulatory network was constructed, including 11 upregulated miRNAs (e.g., miR-200a, miR-200b, and miR-200c) and five downregulated miRNAs (e.g., miR-449a, miR-145-5p, and miR-145-3p). Lymphocyte enhancer factor-1 (LEF1) was predicted to be a target of miR-449a and SOX11 was a target of miR-145-5p. Functional enrichment analyses of these targets were significantly related to the biological process of “negative regulation of transcription from RNA polymerase II promoter” and “positive regulation of transcription from RNA polymerase II promoter” (e.g., NOTCH1, LEF1, and SOX11). In addition, survival analysis showed that miR-449a, miR-145-5p, and LEF1 were approximately correlated with the overall survival prognosis of endometrial cancer patients. Downregulations of miR-449a and miR-145-5p might be involved in the pathogenesis of endometrial cancer and could act as prognostic biomarkers for endometrial cancer patients.

中文翻译：

---

miR-449a和miR-145-5p的下调充当子宫内膜癌的预后生物标志物。

这项研究旨在探讨子宫内膜癌中与预后相关的微小RNA（miRNA）生物标志物。下载了智人miRNA数据集GSE35794和TGGA数据库中的miRNA数据，并使用未配对的t来筛选差异表达的miRNA（DE-miRNA）。-R在limma包中进行测试。基于Venn分析，根据miRWalk筛选重叠的DE-miRNA，并预测其潜在靶标，然后进行靶标功能富集分析和使用Cytoscape可视化的蛋白-蛋白相互作用网络。最后，根据癌症基因组图谱（TCGA）数据库提供的信息，通过生存包对R中的miRNA或靶标与患者预后之间的相关性进行了分析。在子宫内膜样子宫内膜癌样品和子宫内膜样癌之间共鉴定出24个重叠的DE-miRNA。正常样品。然后，构建了miRNA靶标调控网络，包括11个上调的miRNA（例如miR-200a，miR-200b和miR-200c）和5个下调的miRNA（例如miR-449a，miR-145-5p和miR） -145-3p）。淋巴细胞增强因子-1（LEF1）被预测为miR-449a的靶标，而SOX11为miR-145-5p的靶标。这些靶标的功能富集分析与“ RNA聚合酶II启动子转录的负调控”和“ RNA聚合酶II启动子转录的正调控”（例如NOTCH1，LEF1和SOX11）的生物学过程显着相关。此外，生存分析显示miR-449a，miR-145-5p和LEF1与子宫内膜癌患者的整体生存预后大致相关。miR-449a和miR-145-5p的下调可能与子宫内膜癌的发病机制有关，并可能成为子宫内膜癌患者的预后生物标志物。