Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Cell Death Dis. 2023 May 12;14(5):322. doi: 10.1038/s41419-023-05837-6.
Protein arginine methyltransferase 2 (PRMT2) is involved in several biological processes via histone methylation and transcriptional regulation. Although PRMT2 has been reported to affect breast cancer and glioblastoma progression, its role in renal cell cancer (RCC) remains unclear. Here, we found that PRMT2 was upregulated in primary RCC and RCC cell lines. We demonstrated that PRMT2 overexpression promoted RCC cell proliferation and motility both in vitro and in vivo. Moreover, we revealed that PRMT2-mediated H3R8 asymmetric dimethylation (H3R8me2a) was enriched in the WNT5A promoter region and enhanced WNT5A transcriptional expression, leading to activation of Wnt signaling and malignant progression of RCC. Finally, we confirmed that high PRMT2 and WNT5A expression was strongly correlated with poor clinicopathological characteristics and poor overall survival in RCC patient tissues. Our findings indicate that PRMT2 and WNT5A may be promising predictive diagnostic biomarkers for RCC metastasis. Our study also suggests that PRMT2 is a novel therapeutic target in patients with RCC.
蛋白质精氨酸甲基转移酶 2(PRMT2)通过组蛋白甲基化和转录调控参与多种生物学过程。虽然已经报道 PRMT2 影响乳腺癌和神经胶质瘤的进展,但它在肾细胞癌(RCC)中的作用尚不清楚。在这里,我们发现 PRMT2 在原发性 RCC 和 RCC 细胞系中上调。我们证明 PRMT2 过表达促进了体外和体内 RCC 细胞的增殖和迁移。此外,我们揭示了 PRMT2 介导的 H3R8 不对称二甲基化(H3R8me2a)在 WNT5A 启动子区域富集,并增强了 WNT5A 的转录表达,导致 Wnt 信号的激活和 RCC 的恶性进展。最后,我们证实高表达 PRMT2 和 WNT5A 与 RCC 患者组织中不良的临床病理特征和总体生存不良密切相关。我们的研究结果表明,PRMT2 和 WNT5A 可能是 RCC 转移有前途的预测诊断生物标志物。我们的研究还表明,PRMT2 是 RCC 患者的一个新的治疗靶点。