Liao Zhouxiang, Zhang Qi, Yang Lichao, Li Hui, Mo Wanling, Song Zhenyu, Huang Xuejing, Wen Sha, Cheng Xiaojing, He Min
School of Public Health, Guangxi Medical University, Nanning 530021, China.
Laboratory Animal Center, Guangxi Medical University, Nanning 530021, China.
Cancers (Basel). 2023 Dec 27;16(1):129. doi: 10.3390/cancers16010129.
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 and , 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 high expression 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 of had a significantly higher G allele frequency in the East Asian population. Bioinformatics analysis suggested that rs27770 A>G affects mRNA secondary structure and alters the hsa-miR-100-5p/ interaction by forming an additional seedless binding site. This racial variation caused to 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.
肝细胞癌(HCC)在亚洲人群中的发病率和死亡率最高,种族是影响肝癌患者生存时间的独立危险因素。微小RNA(miRNA)在HCC中显著失调,且与HCC预后密切相关。最近的研究表明,不同种族之间的基因变异可能导致HCC miRNA生物标志物的特异性存在差异。在此,我们揭示了一种与HCC预后相关的miRNA——hsa-miR-100-5p的高表达水平,其在携带Polo样激酶1(PLK1)基因变体rs27770A>G的亚洲人群中改善了HCC预后。在本研究中,我们发现hsa-miR-100-5p在多种HCC细胞系中表达下调。虽然模拟物瞬时转染和小鼠肝癌模型证实了hsa-miR-100-5p与[此处原文缺失相关内容]之间的相互作用,但基于癌症基因组图谱肝细胞癌(TCGA-LIHC)数据的分层分析表明,hsa-miR-100-5p低表达水平和[此处原文缺失相关内容]高表达水平均与HCC预后不良相关,尤其是在亚洲人群中。根据千人基因组计划数据库,位于[此处原文缺失相关内容] 3'UTR的单核苷酸多态性(SNP)rs27770在东亚人群中的G等位基因频率显著更高。生物信息学分析表明,rs27770 A>G影响[此处原文缺失相关内容] mRNA二级结构,并通过形成一个额外的无种子结合位点改变hsa-miR-100-5p/[此处原文缺失相关内容]相互作用。这种种族差异导致[此处原文缺失相关内容]更容易受到hsa-miR-100-5p抑制,从而使hsa-miR-100-对亚洲人群的HCC预后更有利。