Department of Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China.
Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Cancer Biother Radiopharm. 2021 Aug;36(6):511-520. doi: 10.1089/cbr.2020.3798. Epub 2020 Jun 23.
This study investigated the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer. The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes. There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients ( < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer. The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer.
本研究旨在探讨 hsa-miR-504 在宫颈癌中的表达及其对宫颈癌进展的可能调控机制。通过分析癌症基因组图谱(TCGA)数据库中 miRNA 的表达,采用 Kaplan-Meier 法分析差异表达 miRNA 与宫颈癌患者总生存期(OS)的相关性。通过 miRWalk 2.0 预测 hsa-miR-504 下游调控的靶基因,进行基因本体论(GO)注释和京都基因与基因组百科全书(KEGG)分析。采用单因素和多因素 Cox 回归筛选预后相关靶基因。在 TCGA 数据库中,宫颈癌与非癌组织之间存在 82 个差异表达 miRNA(fold change >2, < 0.05)。其中,9 个 miRNA,包括 hsa-miR-504,与宫颈癌患者的 OS 显著相关。hsa-miR-504 在宫颈癌中下调,低 hsa-miR-504 表达与预后不良相关。hsa-miR-504 的靶基因有 2670 个,其中 240 个靶基因被 TCGA 数据库进一步证实上调(fold change >2, < 0.05)。GO 和 KEGG 分析显示,上调的靶基因主要富集在细胞周期、DNA 复制、信号通路等。Kaplan-Meier 生存分析显示,21 个靶基因与宫颈癌患者的 OS 相关( < 0.05)。单因素和多因素 Cox 回归分析显示,有 5 个基因是宫颈癌的独立预后因素。hsa-miR-504 的低表达与宫颈癌的发生发展密切相关,hsa-miR-504 可能是宫颈癌患者预后良好的潜在分子标志物。hsa-miR-504 下调参与宫颈癌发生发展的重要机制包括细胞周期、DNA 复制和信号通路。