文章：

hsa-miR-100-5p表达升高改善亚洲人群中携带PLK1变异体rs27770A>G的肝细胞癌预后

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population withPLK1Variant rs27770A>G

原文发布日期：27 December 2023

DOI: 10.3390/cancers16010129

类型: Article

开放获取: 是

英文摘要：

Hepatocellular carcinoma (HCC) has the highest incidence and mortality in the Asian population, and race is an independent risk factor affecting survival time in liver cancer. Micro RNAs (miRNAs) are remarkably dysregulated in HCC and closely associated with HCC prognosis. Recent studies show that genetic variability between ethnic groups may result in differences in the specificity of HCC miRNA biomarkers. Here, we reveal a high expression level of hsa-miR-100-5p, an HCC prognosis-related miRNA, which improves HCC prognosis in the Asian Population with Polo-like kinase 1 (PLK1) variant rs27770A>G. In this study, we discovered that hsa-miR-100-5p was downregulated in various HCC cell lines. While mimics transient transfection and mouse liver cancer model confirmed the interaction between hsa-miR-100-5p andPLK1, a stratified analysis based on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data suggest both low hsa-miR-100-5p expression level and highPLK1expression level associated with poor HCC prognosis, especially in the Asian population. According to the 1000 Genomes Project database, the SNP rs27770 located in 3′UTR ofPLK1had a significantly higher G allele frequency in the East Asian population. Bioinformatics analysis suggested that rs27770 A>G affectsPLK1mRNA secondary structure and alters the hsa-miR-100-5p/PLK1interaction by forming an additional seedless binding site. This racial variation causedPLK1to be more vulnerable to hsa-miR-100-5p inhibition, resulting in hsa-miR-100-5p being more favorable for HCC prognosis in the Asian population.

摘要翻译： 

肝细胞癌（HCC）在亚洲人群中发病率和死亡率最高，种族是影响肝癌生存时间的独立危险因素。微小RNA（miRNA）在HCC中显著失调，并与HCC预后密切相关。近期研究表明，不同种族间的遗传变异可能导致HCC miRNA生物标志物特异性存在差异。本文揭示了一种与HCC预后相关的miRNA——hsa-miR-100-5p的高表达水平，该分子通过Polo样激酶1（PLK1）基因变异rs27770A>G改善亚洲人群的HCC预后。研究发现hsa-miR-100-5p在多种HCC细胞系中表达下调，通过模拟物瞬时转染和小鼠肝癌模型证实了hsa-miR-100-5p与PLK1的相互作用。基于癌症基因组图谱肝细胞癌（TCGA-LIHC）数据的分层分析表明，低hsa-miR-100-5p表达水平和高PLK1表达水平均与不良HCC预后相关，尤其在亚洲人群中更为显著。根据千人基因组计划数据库，位于PLK1基因3′UTR区的SNP rs27770在东亚人群中G等位基因频率显著更高。生物信息学分析提示，rs27770 A>G变异通过形成额外的无种子结合位点，影响PLK1 mRNA二级结构并改变hsa-miR-100-5p/PLK1相互作用。这种种族特异性变异使PLK1更易受hsa-miR-100-5p抑制，从而导致hsa-miR-100-5p在亚洲人群中更有利于改善HCC预后。

原文链接：

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population withPLK1Variant rs27770A>G