Protein arginine methyltransferases (PRMTs) have been implicated in the development of various cancers. PRMT2, a member of the type I PRMT family, is overexpressed in multiple tumors. However, the expression and role of PRMT2 in hepatocellular carcinoma (HCC) have not been studied. Here, we discovered that PRMT2 expression is elevated in HCC tissues compared to the corresponding non-tumor tissues, and PRMT2 overexpression is an independent predictor of poor prognosis in HCC patients. Depletion of PRMT2 in HCC cell lines inhibited their cell growth and induced apoptosis. Mechanistic investigations showed that PRMT2 is responsible for H3R8 asymmetric methylation (H3R8me2a). H3R8me2a enrichment at the Bcl2 promoter increases its accessibility to STAT3, promoting Bcl2 gene expression. In addition, our results confirmed that the catalytically inactive mutant of PRMT2 or the type I PRMT inhibitor MS023 impaired the pro-tumorigenic functions of PRMT2 in HCC cells. Overall, our findings showed that PRMT2 functions as an oncogenic gene in HCC, revealing its potential as a novel therapeutic target in HCC.

蛋白精氨酸甲基转移酶（PRMTs）已牵涉到各种癌症的发展。PRMT2是I型PRMT家族的成员，在多种肿瘤中过表达。但是，尚未研究PRMT​​2在肝细胞癌（HCC）中的表达和作用。在这里，我们发现与相应的非肿瘤组织相比，PRMT2表达在HCC组织中升高，并且PRMT2的过表达是HCC患者预后不良的独立预测因子。HMT细胞系中PRMT2的耗竭抑制了它们的细胞生长并诱导了细胞凋亡。机理研究表明PRMT2负责H3R8不对称甲基化（H3R8me2a）。H3R8me2a在Bcl2启动子上的富集增加了它对STAT3的可及性，从而促进了Bcl2基因表达。此外，我们的结果证实PRMT2的催化失活突变体或I型PRMT抑制剂MS023损害了HMT细胞中PRMT2的促癌作用。总体而言，我们的发现表明PRMT2在HCC中起着致癌基因的作用，揭示了其作为HCC新型治疗靶标的潜力。