Novel molecular mechanisms of immune evasion in hepatocellular carcinoma: NSUN2‐mediated increase of SOAT2 RNA methylation

作者：Jinhua Jiang, Feng Liu, Dan Cui, Caixia Xu, Jiachang Chi, Tinghua Yan, Fang Guo · 发表于：癌症：英文版 · 年份：2025 · DOI：10.1002/cac2.70023 · 被引用次数：20 · 研究领域：RNA modifications and cancer、Epigenetics and DNA Methylation、RNA Research and Splicing

Abstract Background Hepatocellular carcinoma (HCC) is a deadly malignancy known for its ability to evade immune surveillance. NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an RNA methyltransferase involved in carcinogenesis, has been associated with immune evasion and energy metabolism reprogramming. This study aimed to examine the molecular mechanisms underlying the involvement of NSUN2 in immune evasion and metabolic reprogramming of HCC. Methods Single‐cell transcriptomic sequencing was applied to examine cellular composition changes, particularly immune cell dynamics, in HCC and adjacent normal tissues. Bulk RNA‐seq and proteomics identified key genes and proteins. Methylation sequencing and methylated RNA immunoprecipitation (MeRIP) were carried out to characterize the role of NSUN2 in 5‐methylcytosine (m5C) modification of sterol O‐acyltransferase 2 ( SOAT2 ). Clinical samples from 30 HCC patients were analyzed using reverse transcription‐quantitative polymerase chain reaction and Western blotting. Gene expression was manipulated using CRISPR/Cas9 and lentiviral vectors. In vitro co‐culture models and metabolomics were used to study HCC cell‐T cell interactions, energy metabolism, and immune evasion. Tumor growth in an orthotopic mouse model was monitored by bioluminescence imaging, with subsequent measurements of tumor weight, volume, and immunohistochemical staining. Results Single‐cell transcriptomic analysis identified a marked increase in malignant cells ...