Single-cell and spatial transcriptomics reveal correlation between RNA methylation-related miRNA risk model and immune infiltration in hepatocellular carcinoma

作者：Rong Su, Yong Du, Pan Tian, Weifang Ma, Yongfeng Hui, Shaoqi Yang · 发表于：Frontiers in Oncology · 年份：2025 · DOI：10.3389/fonc.2025.1553239 · 被引用次数：4 · 研究领域：MicroRNA in disease regulation、Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research

Introduction Increasing evidence highlights the pivotal role of RNA methylation and miRNAs in hepatocellular carcinoma (HCC). However, the risk associated with RNA methylation-related miRNAs (RMRMs) in the HCC immune microenvironment remains largely unknown. Here, we predicted the correlation between RMRM risk and immune cell infiltration in HCC using machine learning. Methods MiRNA sequencing data was used to identify RMRMs. A risk score model of HCC was developed utilizing four RMRMs, including miR-551a, miR-4739, miR-326, and miR-210-3p. Results Patients with high-risk scores exhibited poorer prognoses. Single-cell RNA sequencing (scRNA-seq) analysis revealed the high-risk group exhibited increased infiltration levels of several immune cell subtypes, including myeloid-derived suppressor cell (MDSC), macrophage, and T cells. The data integration of scRNA-seq and bulk RNA-seq showed the decreased TIDE score in the high-risk patients and the elevated levels of Macro-secreted phosphoprotein 1 (SPP1), MDSC-meiotic nuclear divisions 1 (MND1), γδ T cells, and Macro-complement C1q C chain (C1QC) predicted adverse prognosis. ScRNA-seq and spatial transcriptomics data integration unveiled the spatial distribution of RMRMs risk scores and their correlation with immune cell subtype localization. Risk model-based clustering of HCC samples revealed that cluster 2, characterized by a higher risk score, correlated with a poorer prognosis and reduced immune and stromal scores. In vitro, th...