Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
Int J Med Sci. 2021 Aug 27;18(15):3588-3598. doi: 10.7150/ijms.62467. eCollection 2021.
: 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. 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. 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 , 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. 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.
蛋白精氨酸甲基转移酶 4（PRMT4）已被报道在几种常见癌症中发挥作用；然而，PRMT4 在肝细胞癌（HCC）中的功能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。通过免疫组织化学分析 140 例患者样本的 HCC 组织微阵列（TMA），研究了 PRMT4 的表达和临床病理特征。使用 CCK-8、结晶紫和 Transwell 测定法，研究了过表达或下调 PRMT4 的 HCC 细胞系的细胞增殖、集落形成、迁移和侵袭。通过 Western blot 测定法探讨了 PRMT4 功能的潜在机制。与相邻非肿瘤组织相比，PRMT4 在 HCC 肿瘤组织中高表达。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著相关。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 过表达促进 HCC 细胞增殖、迁移和侵袭，而敲低 PRMT4 则抑制这些恶性行为。进一步的结果表明，PRMT4 通过激活 AKT/mTOR 信号通路促进 HCC 细胞的进展。此外，MK2206 或雷帕霉素抑制 AKT/mTOR 信号通路显著减弱了 PRMT4 介导的恶性表型。本研究表明，PRMT4 通过激活 AKT/mTOR 信号通路可能促进 HCC 细胞的进展，这可能是 HCC 的一个有价值的生物标志物和潜在靶点。
