NSUN2-mediated mRNA m5C Modification Regulates the Progression of Hepatocellular Carcinoma

Abstract

RNA modification affects many biological processes and physiological diseases. The 5-methylcytosine (m5C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m5C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that a major fraction of the hypermethylated genes participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m5C methyltransferase NSUN2 was highly expressed in HCC tissues consistently. Interestingly, the expression of many oncogenes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNA of GRB2, RNF115, and AATF decreased significantly with the depletion of NSUN2 in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Our study demonstrated a vital role of NSUN2 in the progression of HCC.