NOP2/Sun domain 4-mediated m5C methylation of Janus kinase 1 promotes hepatocellular carcinoma progression

5-methylcytosine (m5C) modification is associated with various cancers, but the role of NOP2/Sun domain 4 (NSUN4)-mediated m5C modification in hepatocellular carcinoma (HCC) remains unclear. Here, NSUN4 was markedly upregulated in HCC and correlated with poor survival. Silencing NSUN4 suppressed HCC cell proliferation, migration, invasion and tumor growth. Mechanistically, NSUN4 enhanced JAK1 mRNA stability and expression through m5C methylation, activating JAK-STAT3 signaling and driving malignant progression. Thus, NSUN4 promotes HCC progression via m5C-dependent JAK1 stabilization and JAK-STAT3 activation, highlighting NSUN4 as a promising therapeutic target for HCC.