PRMT2 promotes RCC tumorigenesis and metastasis via enhancing WNT5A transcriptional expression

Abstract

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.

Protein arginine N-methyltransferase 2 plays a noncatalytic role in the histone methylation activity of PRMT1

“…5 B ). PRMT2 has been implicated either directly or indirectly with H3R8 methylation ( 12 , 13 , 14 ). It is possible that there may be conditions that enhance the catalytic activity of PRMT2 such that it can methylate H3R8 in a biologically relevant timeframe, but these conditions have yet to be identified and replicated in vitro .…”

“…Despite such low in vitro activity, paradoxically PRMT2 was shown to facilitate aDMA formation on histone H3 at arginine 8 (H3R8me2a) at promoter sites for transcriptional activation during Xenopus development ( 11 ). It was later demonstrated that PRMT2 overexpression and the H3R8me2a mark were linked to oncogenic transcriptional programming in glioblastoma multiforme, hepatocellular carcinoma, and renal cell carcinoma, in each case strongly correlating with disease severity ( 12 , 13 , 14 ). In this regard, PRMT2 joins the PRMT pantheon of other well-known writers with oncogenic capacity ( 15 , 16 ).…”

PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis

“…Cell Counting Kit-8 (CCK-8, VC5001L-500T, VICMID) and colony formation assays was used for proliferation analysis [ 23 ], shown as in Supplementary Materials and Methods .…”

Resistance to 2-Hydroxy-Flutamide in Prostate Cancer Cells Is Associated with the Downregulation of Phosphatidylcholine Biosynthesis and Epigenetic Modifications

“…Thus, the tumor cell microenvironment, including the presence of flutamide in the medium, could induce an epigenetic regulation that triggers a phenotypic transition towards metabolically dormant cells with stem cell-like properties, characterized by low metabolic activity and drug resistance. We then determined the expression of the protein arginine N-methyltransferase 2 (PRMT2) that catalyzes arginine methylation in proteins, including those involved in epigenetic regulation [29]. The protein as well as mRNA levels of PRMT2 were decreased in the LN-FLU cells compared to the LNCaP cells (Figure 4B), suggesting a reduction in protein methylation.…”