Objectives: Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma (HCC). However, clinical significance of miR-5010-3p in HCC is not elucidated. This study aims to explore the prognostic value and role of miR-5010-3p in HCC.
Methods: The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis. The Kaplan-Meier, Cox univariate, and Cox multivariate analysis were used to predict its role in the prognosis of HCC. The downstream target genes were predicted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the potential functional pathways they may participate in. Finally, methyl thiazolyl tetrazolium (MTT) assay and 5-ethyl-2'-deoxyuridine (EDU) incorporation experiment were carried out to prove its effect on proliferation.
Results: The expression of miR-5010-3p was associated with histological grade (P=0.019), vascular invasion degree (P=0.049), TP53 level (P=0.004), and alpha fetoprotein (AFP) level (P=0.012). A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve (AUC: 0.712, 95% CI 0.649 to 0.776). High expression of miR-5010-3p was associated with shorter overall survival (OS) (P=0.003). The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process. In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells.
Conclusions: MiR-5010-3p promotes the proliferation of liver cancer cells, and its high expression is associated with poor prognosis, which may be a potential prognostic marker.
目的: 许多miRNA在肝细胞癌(hepatocellular carcinoma，HCC)中异常表达，然而miR-5010-3p在HCC中的临床意义尚不清楚。本研究旨在探讨miR-5010-3p在预测HCC预后中的价值和作用。方法: 基于癌症基因组图谱(the Cancer Genome Atlas，TCGA)数据库分析miR-5010-3p在HCC中的差异基因表达。采用受试者操作特征(receiver operating characteristic，ROC)曲线评估miR-5010-3p表达水平对HCC预后的预测价值；采用Kaplan-Meier、Cox单因素和Cox多因素分析其在预测HCC预后中的作用。预测下游靶基因，并进行基因本体(gene ontology，GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)分析，预测其可能参与的潜在功能通路。最后通过四甲基偶氮唑蓝比色法(methyl thiazolyl tetrazolium，MTT)和5-乙炔基-2’脱氧尿嘧啶核苷(5-ethyl-2’- deoxyuridine，EdU)掺入实验验证其对细胞增殖的影响。结果: MiR-5010-3p的表达与组织学分级(P=0.019)、血管侵犯程度(P=0.049)、TP53水平(P=0.004)和甲胎蛋白水平(P=0.012)有关。ROC曲线结果表明miR-5010-3p可作为HCC和非肿瘤组织的标志物(AUC：0.712，95% CI 0.649~0.776)。MiR-5010-3p高表达与较短的总生存期(overall survival，OS)相关(P=0.003)。功能富集分析显示miR-5010-3p与肿瘤发生过程相关。体外实验证明miR-5010-3p可促进肝癌细胞增殖。结论: MiR-5010-3p可促进肝癌细胞增殖，且其高表达与不良预后相关，可能是一种潜在的预后标志物。.
目的: 许多miRNA在肝细胞癌(hepatocellular carcinoma，HCC)中异常表达，然而miR-5010-3p在HCC中的临床意义尚不清楚。本研究旨在探讨miR-5010-3p在预测HCC预后中的价值和作用。
方法: 基于癌症基因组图谱(the Cancer Genome Atlas，TCGA)数据库分析miR-5010-3p在HCC中的差异基因表达。采用受试者操作特征(receiver operating characteristic，ROC)曲线评估miR-5010-3p表达水平对HCC预后的预测价值；采用Kaplan-Meier、Cox单因素和Cox多因素分析其在预测HCC预后中的作用。预测下游靶基因，并进行基因本体(gene ontology，GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)分析，预测其可能参与的潜在功能通路。最后通过四甲基偶氮唑蓝比色法(methyl thiazolyl tetrazolium，MTT)和5-乙炔基-2’脱氧尿嘧啶核苷(5-ethyl-2’- deoxyuridine，EdU)掺入实验验证其对细胞增殖的影响。
结果: MiR-5010-3p的表达与组织学分级(P=0.019)、血管侵犯程度(P=0.049)、TP53水平(P=0.004)和甲胎蛋白水平(P=0.012)有关。ROC曲线结果表明miR-5010-3p可作为HCC和非肿瘤组织的标志物(AUC：0.712，95% CI 0.649~0.776)。MiR-5010-3p高表达与较短的总生存期(overall survival，OS)相关(P=0.003)。功能富集分析显示miR-5010-3p与肿瘤发生过程相关。体外实验证明miR-5010-3p可促进肝癌细胞增殖。
结论: MiR-5010-3p可促进肝癌细胞增殖，且其高表达与不良预后相关，可能是一种潜在的预后标志物。
Keywords: biomarker; hepatocellular carcinoma; miR-5010-3p; prognosis; the Cancer Genome Atlas.