| The protein arginine methyltransferase 4(PRMT4)is also called coactivator-associated arginine methyltransferase(CARM1),which is capable of asymmetric dimethylated protein substrates and has a co-activation effect on various nuclear receptors and transcription factors.PRMT4 is overexpressed in a variety of tumors,promoting the growth and metastasis of tumor cells.At present,the role and mechanism of PRMT4 in the occurrence and development of gastric cancer have not been reported,this subject will go into in-depth research on this.In the first part of this study,the expression level of PRMT4 in 32 specimens of gastric cancer and adjacent tissues were measured by immunohistochemistry technology.The results showed that PRMT4 was overexpressed in gastric cancer tissues and was positively correlated with the presence of lymph node metastasis in patients with gastric cancer.Further analysis using public databases TCGA,Oncomine,and Kaplan-Meier Plotter data revealed that PRMT4 is highly expressed in gastric cancer,and the survival time of gastric cancer patients with high expression of PRMT4 is significantly shortened.In the second part of this study,we changed the expression of PRMT4 in gastric cancer cell lines through plasmid-mediated interference technology and plasmid overexpression technology.Cell biology methods,such as CCK8 assay,colony formation assay,flow cytometry,scratch healing experiment and transwell assay were used to study the function of PRMT4 in gastric cancer.It was found that the proliferation,colony formation,migration and invasion ability of gastric cancer cells were inhibited;the cell apoptosis was induced by silencing of PRMT4.The proliferation,colony formation,migration and invasion ability of gastric cancer cells were induced;the cell apoptosis was inhibited by overexpressed PRMT4.In the third part of this study,we further explored the related molecular mechanism of PRMT4.By luciferase report experiment and real-time PCR assay,we found that down-regulating the expression of PRMT4 can inhibit TCF(T cell factor)transcriptional activity and reduce the expression of downstream target genes(C-myc,Cyclin D1,Survivin,MMP-7,Lef1 and Axin2)of the Wnt/β-catenin signaling pathway.Furthermore,western blot results showed that changes in PRMT4 level affect the expression of Wnt/β-catenin signaling pathway-related proteins(activatedβ-catenin,p-GSK3β,C-myc,and N-cadherin).In summary,PRMT4 is overexpressed in gastric cancer,which promotes the growth and metastasis of gastric cancer cells,and may participate in the development of gastric cancer through the Wnt/β-catenin signaling pathway.PRMT4 can be a potential therapeutic target for gastric cancer,providing new ideas for clinical treatment of gastric cancer. |
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