Hu Tao, Gu Jiarong, Tan Lin, Deng Haiyan, Gao Xianxian, Yang Shanru, Xu Hao, Hou Xin, Liao Qi, Yang Xiaoping
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, PR China.
School of Public Health, Ningxia Medical University, Yinchuan, Ningxia, PR China; Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, PR China.
Int Immunopharmacol. 2025 Jan 27;146:113850. doi: 10.1016/j.intimp.2024.113850. Epub 2024 Dec 16.
MicroRNAs play a significant role in the initiation and progression of hepatocellular carcinoma (HCC); however, their roles in immune regulation of HCC remain unclear. Our study aimed to identify an immune-related miRNA signature and explore its impact on the prognosis and tumor immune microenvironment HCC. Initially, we identified 48 differentially expressed immune-related miRNAs. Using the LASSO regression dimensionality reduction method, we constructed an immune-related miRNA signature from 12 of these miRNAs. This signature has emerged as an independent prognostic marker and is associated with the clinical stage of HCC. To elucidate the roles of the twelve-microRNA signature, we predicted their target genes. Enrichment analysis indicated that these target genes were involved in immune cell infiltration. Notably, the target genes regulated by hsa-miR-139-5p, hsa-miR-551a, and hsa-miR-7-5p showed a partial overlap. We further confirmed the differential expression of miR-7, miR-551a, miR-139-5p, and some of their overlapping target genes in tumor and non-tumor tissues derived from patients with HCC using RT-qPCR. Overall, we identified an immune-related miRNA signature that is strongly correlated with the prognosis and immune microenvironment of HCC; and confirmed the differential expression of the three most important microRNAs and their overlapping target genes in tumor and non-tumor tissues derived from HCC patients.
微小RNA在肝细胞癌(HCC)的发生和发展中起重要作用;然而,它们在HCC免疫调节中的作用仍不清楚。我们的研究旨在识别一种与免疫相关的微小RNA特征,并探讨其对HCC预后和肿瘤免疫微环境的影响。最初,我们鉴定出48种差异表达的免疫相关微小RNA。使用套索回归降维方法,我们从其中12种微小RNA构建了一种与免疫相关的微小RNA特征。该特征已成为一个独立的预后标志物,并与HCC的临床分期相关。为了阐明这12种微小RNA特征的作用,我们预测了它们的靶基因。富集分析表明这些靶基因参与免疫细胞浸润。值得注意的是,由hsa-miR-139-5p、hsa-miR-551a和hsa-miR-7-5p调控的靶基因存在部分重叠。我们使用RT-qPCR进一步证实了miR-7、miR-551a、miR-139-5p及其一些重叠靶基因在HCC患者肿瘤和非肿瘤组织中的差异表达。总体而言,我们识别出一种与HCC预后和免疫微环境密切相关的免疫相关微小RNA特征;并证实了三种最重要的微小RNA及其重叠靶基因在HCC患者肿瘤和非肿瘤组织中的差异表达。