Abstract: Objective · To investigate the effect of protein arginine methyltransferase 4 (PRMT4) on the development and progression of gastric carcinoma and the underlying molecular mechanisms. Methods · The expression levels of PRMT4 in 32 specimens of gastric cancer and adjacent tissues were measured by immunohistochemistry technology. Public databases were used to analyze the expression of PRMT4 in gastric cancer and its effect on the survival of patients with gastric cancer. PRMT4 expressions of gastric cancer MGC-803 and MKN-45 cells were down-regulated by short hairpin RNA-mediated knockdown, and PRMT4 expression of gastric cancer SGC-7901 cells was up-regulated by using plasmid-mediated overexpression. Cell biology methods, such as MTT assay, colony formation assay, flow cytometry, and Transwell assay were used to study the effect of PRMT4 on proliferation, apoptosis, migration and invasion of gastric cancer cells. Luciferase reporter assay was used to detect transcription activity of endogenous transcription factor TCF (T cell factor) after PRMT4 silencing. The mRNA level changes of Wnt/β-catenin pathway downstream target genes after PRMT4 silencing were detected by real-time PCR. The protein level changes of Wnt/β-catenin pathway-related proteins after PRMT4 silencing and overexpression were detected by Western blotting. Results · PRMT4 was highly expressed in gastric cancer tissues. Patients with higher expression of PRMT4 had shorter survival than those with lower expression of PRMT4. The proliferation, colony formation, migration and invasion ability of gastric cancer cells were inhibited; the cell apoptosis was induced by silencing of PRMT4. The Wnt/β-catenin signaling pathway was also inhibited by PRMT4 knockdown. The proliferation, colony formation, migration and invasion ability of gastric cancer cells were induced; the cell apoptosis was inhibited by overexpressed PRMT4. The Wnt/β-catenin signaling pathway was also activated by PRMT4 overexpression. Conclusion · PRMT4 is highly expressed in gastric cancer. It can promote the growth, migration and invasion of gastric cancer cells through Wnt/β-catenin signaling pathway.

Key words: protein arginine methyltransferase 4 (PRMT4), gastric cancer, proliferation, Wnt/β-catenin signaling pathway