PDF(Pubmed)
Abstract：
OBJECTIVE: miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets.
RESULTS: In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.
RESULTS: In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.
摘要：
目的：miR-497/195位于17p13.1，是一个高度保守的miRNA簇，其异常表达是癌变的关键调节因子。我们使用公开可用的数据集对miR-497/195簇进行了全面分析，以确定其在宫颈癌（CC）中的预后效用和作用。
结果：计算机模拟分析和验证表明，该集群在CC中下调。miR-497/195簇的总共60个靶基因被鉴定为在正常和CC样品之间差异表达。ShinyGO,STRING,CytoHubba,定时器2.0,HPA,和HCMBD用于功能富集，PPIN网络建设,枢纽基因鉴定，免疫浸润相关性，组织病理学表达，并测定miR-497/195簇及其靶基因的转移潜能。PPIN分析确定CCNE1、CCNE2、ANLN、RACGAP1,KIF23,CHEK1,CDC25A,E2F7、CDK1和CEP55是前10个hub基因(HG)。此外，RECK的上调,ATD5和BCL2、OSBPL3、RCAN3和HIST1H3H的下调影响CC患者的总生存期。我们确定了6个目标(TFAP2A，CLSPN,RASEF,HIST1H3H,AKT3,和ITPR1)对miR-497/195簇转移的影响。此外,还鉴定了8个可药用基因和38种潜在药物。我们的研究确定了miR-497/195簇靶基因和途径，可用于CC的预后和治疗应用。
结果：计算机模拟分析和验证表明，该集群在CC中下调。miR-497/195簇的总共60个靶基因被鉴定为在正常和CC样品之间差异表达。ShinyGO,STRING,CytoHubba,定时器2.0,HPA,和HCMBD用于功能富集，PPIN网络建设,枢纽基因鉴定，免疫浸润相关性，组织病理学表达，并测定miR-497/195簇及其靶基因的转移潜能。PPIN分析确定CCNE1、CCNE2、ANLN、RACGAP1,KIF23,CHEK1,CDC25A,E2F7、CDK1和CEP55是前10个hub基因(HG)。此外，RECK的上调,ATD5和BCL2、OSBPL3、RCAN3和HIST1H3H的下调影响CC患者的总生存期。我们确定了6个目标(TFAP2A，CLSPN,RASEF,HIST1H3H,AKT3,和ITPR1)对miR-497/195簇转移的影响。此外,还鉴定了8个可药用基因和38种潜在药物。我们的研究确定了miR-497/195簇靶基因和途径，可用于CC的预后和治疗应用。
