子宫内膜癌组织中PRMT2高表达及其促进细胞增殖的机制探讨

High expression of PRMT2 in endometrial carcinoma tissues and its mechanism of promoting cell proliferation

目的:探究蛋白质精氨酸甲基转移酶2(protein arginine methyltransferase 2,PRMT2)在子宫内膜癌恶性进展中的作用及临床意义。方法:免疫组化方法检测子宫内膜癌组织及其癌旁组织中PRMT2的表达。通过感染PRMT2 shRNA慢病毒和转染pcDNA3.1-PRMT2质粒,构建子宫内膜癌HEC-1A细胞PRMT2敲低和过表达模型,CCK-8和克隆形成实验检测PRMT2对细胞增殖的影响。通过RT-qPCR探明PRMT2下游靶基因,并采用Western blot实验进行验证。采用挽救实验证实PRMT2调控靶基因的特异性和在子宫内膜癌增殖中的重要性。结果:免疫组化实验发现PRMT2在子宫内膜癌组织中表达明显高于癌旁组织,且PRMT2表达与患者生存期呈显著负相关(P<0.05)。敲低PRMT2表达能显著抑制子宫内膜癌细胞增殖(P<0.05),并且发现PRMT2敲低可以抑制CCND1表达;相反,过表达PRMT2能够促进子宫内膜癌细胞增殖(P<0.05),促进CCND1表达。挽救实验结果表明,在PRMT2敲低的细胞中过表达CCND1能够部分恢复细胞的增殖能力。结论:PRMT2在子宫内膜癌组织中高表达,并且PRMT2能够通过调控CCND1表达促进子宫内膜癌细胞的增殖。

Objective:To investigate the role and clinical significance of protein arginine methyltransferase 2(PRMT2)in the malignant progression of endometrial cancer.Methods:The expression of PRMT2 in endometrial cancer tissues and adjacent tissues was detected by immunohistochemistry.By infecting PRMT2 shRNA lentivirus and transfecting pcDNA3.1-PRMT2 plasmid,the cell model of PRMT2 knockdown and overexpression was constructed.CCK-8 and clone formation experiments were used to detect the effects of PRMT2 on cell proliferation.The downstream target gene of PRMT2 was identified by RT-qPCR and verified by Western blot.In addition,rescue experiments will be used to confirm the specificity of PRMT2's regulation of target genes and their importance in endometrial cancer proliferation.Results:Immunohistochemical experiments showed that the expression of PRMT2 in endometrial cancer tissues was significantly higher than that in adjacent tissues,and the expression of PRMT2 was significantly negatively correlated with patient survival(P<0.05).Knockdown of PRMT2 expression can significantly inhibit the proliferation of endometrial cancer cells(P<0.05),and it has been found that knockdown of PRMT2 can suppress the expression of CCND1.On the contrary,overexpression of PRMT2 can promote cell proliferation(P<0.05)and CCND1 expression.Rescue experiments showed that overexpressing CCND1 in PRMT2-knockdown cells can partially restore cell proliferation.Conclusion:PRMT2 is highly expressed in endometrial cancer,and PRMT2 can promote the proliferation of endometrial cancer cells by regulating CCND1 expression.