Background: Protein arginine methyltransferase 4 (PRMT4) has been reported to play a role in several common cancers; however, the function and mechanism of PRMT4 in hepatocellular carcinoma (HCC) are not fully understood. This study aimed to investigate the role and mechanism of PRMT4 in the progression of HCC. Methods: PRMT4 expression and clinicopathological characteristics were investigated using an HCC tissue microarray (TMA) consisting of 140 patient samples analyzed by immunohistochemistry. CCK-8, crystal violet and Transwell assays were used to determine cell proliferation, colony formation, migration, and invasion of HCC cell lines in which PRMT4 was overexpressed or downregulated. The underlying mechanism of PRMT4 function was explored by Western blot assays. Results: PRMT4 was highly expressed in HCC tumor tissues compared to adjacent nontumor tissues. PRMT4 expression was significantly associated with alpha-fetoprotein levels, tumor size, satellite nodules, and microvascular invasion. Patients with higher PRMT4 expression had a shorter survival time and higher recurrence rate. Functional studies demonstrated that PRMT4 overexpression promoted HCC cell proliferation, migration, and invasion in vitro, while knocking down PRMT4 inhibited these malignant behaviors. Additional results revealed that PRMT4 promoted the progression of HCC cells via activation of the AKT/mTOR signaling pathway. Furthermore, inhibition of the AKT/mTOR signaling by MK2206 or rapamycin significantly attenuated PRMT4-mediated malignant phenotypes. Conclusions: This study suggests that PRMT4 may promote the progression of HCC cells by activating the AKT/mTOR signaling pathway, which may be a valuable biomarker and potential target for HCC.

中文翻译：

---

PRMT4 通过激活 AKT/mTOR 信号促进肝细胞癌进展，并表明预后不良。

背景：据报道，蛋白质精氨酸甲基转移酶 4 (PRMT4) 在几种常见癌症中发挥作用。然而，PRMT4在肝细胞癌（HCC）中的作用和机制尚不完全清楚。本研究旨在探讨PRMT4在HCC进展中的作用和机制。方法：使用 HCC 组织微阵列 (TMA) 研究 PRMT4 表达和临床病理学特征，该微阵列由 140 个通过免疫组织化学分析的患者样本组成。CCK-8、结晶紫和 Transwell 测定用于确定 PRMT4 过表达或下调的 HCC 细胞系的细胞增殖、集落形成、迁移和侵袭。通过蛋白质印迹分析探索了 PRMT4 功能的潜在机制。结果：与邻近的非肿瘤组织相比，PRMT4 在 HCC 肿瘤组织中高度表达。PRMT4 表达与甲胎蛋白水平、肿瘤大小、卫星结节和微血管侵犯显着相关。PRMT4表达较高的患者生存时间较短，复发率较高。功能研究表明，PRMT4 过表达在体外促进 HCC 细胞增殖、迁移和侵袭，而敲除 PRMT4 抑制这些恶性行为。其他结果表明，PRMT4 通过激活 AKT/mTOR 信号通路促进 HCC 细胞的进展。此外，MK2206 或雷帕霉素对 AKT/mTOR 信号传导的抑制显着减弱了 PRMT4 介导的恶性表型。结论：