PRMT5在结直肠癌中的表达及其对结直肠癌细胞增殖能力的影响
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摘要
目的:检测结直肠癌(colorectalcancer,CRC)中蛋白质精氨酸甲基转移酶-5(proteinargininemethyltransferase5,PRMT5)的表达,探讨其表达与临床病理参数的关系,并观察PRMT5表达敲低后对CRC细胞增殖能力的影响。方法:采用免疫组织化学的方法检测53例CRC肿瘤组织及18例癌旁正常组织中PRMT5的表达情况;利用特异siRNA分别敲低CRC细胞系HCT116和SW620细胞中PRMT5表达后,采用CCK-8试验检测PRMT5敲低后HCT116和SW620细胞增殖能力的改变;利用流式细胞术检测PRMT5敲低后HCT116和SW620细胞的周期变化情况。结果:PRMT5在CRC中的表达阳性率为88.68%,显著高于癌旁正常组织(P<0.01)。PRMT5在CRC组织中的表达与患者性别、年龄、淋巴结转移、远端转移等无关(P>0.05),但与肿瘤分化程度密切相关(P<0.05);敲低PMRT5表达后,HCT116和SW620细胞的增殖能力显著降低(P<0.01)。并且,敲低PRMT5表达会导致HCT116和SW620细胞被阻滞在G0/G1期(P<0.01)。结论:与癌旁正常组织相比,PRMT5在CRC肿瘤组织中表达显著上升,敲低PRMT5表达会抑制CRC细胞增殖,表明PRMT5可能在促进CRC细胞生长和癌症演变进程中发挥重要作用。
Objective: To explore the expression of protein arginine methyltransferase 5(PRMT5) in colorectal cancer and normal tissues and the relationship between the clinical characteristics and the expression of PRMT5, and to investigate the proliferation of colorectal cancer cells when PRMT5 was knocked down. Methods: Expression of PRMT5 in colorectal cancer and normal tissues was detected by immunohistochemical staining. PRMT5 were knocked down by small interfering RNA(siRNA). The proliferation of HCT116 and SW620 cells was evaluatedby cell counting kit-8(CCK-8) assay. The changes of cell cycle of HCT116 and SW620 cells were detected by flow cytometry when PRMT5 was knocked down. Results: The positive expression rate of PRMT5 in colorectal cancer tissues was 88.68%, which was higher than that in normal colorectal tissues(P<0.01). The expression of PRMT5 was associated with differentiation(P<0.05), but not with the gender, age, lymph node metastasis and distant metastasis etc.(P>0.05). The proliferation of HCT116 and SW620 cells were significantly inhibited when PRMT5 was knocked down by siRNA(P<0.01). The HCT116 and SW620 cells were arrested in G0/G1 phase when PRMT5 was knocked down(P<0.05). Conclusion: The expression of PRMT5 in colorectal cancer was significantly increased in comparison with normal tissues, and it may play important roles in promoting cell proliferation and the evolution of colorectal cancer.
Objective: To explore the expression of protein arginine methyltransferase 5(PRMT5) in colorectal cancer and normal tissues and the relationship between the clinical characteristics and the expression of PRMT5, and to investigate the proliferation of colorectal cancer cells when PRMT5 was knocked down. Methods: Expression of PRMT5 in colorectal cancer and normal tissues was detected by immunohistochemical staining. PRMT5 were knocked down by small interfering RNA(siRNA). The proliferation of HCT116 and SW620 cells was evaluatedby cell counting kit-8(CCK-8) assay. The changes of cell cycle of HCT116 and SW620 cells were detected by flow cytometry when PRMT5 was knocked down. Results: The positive expression rate of PRMT5 in colorectal cancer tissues was 88.68%, which was higher than that in normal colorectal tissues(P<0.01). The expression of PRMT5 was associated with differentiation(P<0.05), but not with the gender, age, lymph node metastasis and distant metastasis etc.(P>0.05). The proliferation of HCT116 and SW620 cells were significantly inhibited when PRMT5 was knocked down by siRNA(P<0.01). The HCT116 and SW620 cells were arrested in G0/G1 phase when PRMT5 was knocked down(P<0.05). Conclusion: The expression of PRMT5 in colorectal cancer was significantly increased in comparison with normal tissues, and it may play important roles in promoting cell proliferation and the evolution of colorectal cancer.
引文
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9.许婷,曹仁贤.蛋白质精氨酸甲基转移酶家族与肿瘤的关系[J].现代医药卫生,2015,31(1):67-70.XU Ting,CAO Renxian.Protein arginine methyltransferases and cancer[J].Modern Medicine Health,2015,31(1):67-70.
10.文君,闵雪洁,赵丽,等.蛋白质精氨酸甲基转移酶在肿瘤中的作用及机制研究进展[J].上海交通大学学报(医学版),2017,37(6):842-846.WEN Jun,MIN Xuejie,ZHAO Li,et al.Research progress of e?ect and mechanism of protein arginine methyltransferase in tumors[J].Journal of Shanghai Jiao Tong University.Medical Science,2017,37(6):842-846.
2.Chen W,Zheng R,Baade PD,et al.Cancer statistics in China[J].CACancer J Clin,2016,66(2):115-132.
3.Karkhanis V,Hu YJ,Baiocchi RA,et al.Versatility of PRMT5-induced methylation in growth control and development[J].Trends Biochem Sci,2011,36(12):633-641.
4.Stopa N,Krebs JE,Shechter D.The PRMT5 arginine methyltransferase:many roles in development,cancer and beyond[J].Cell Mol Life Sci,2015,72(11):2041-2059.
5.Blanc RS,Richard S.Arginine methylation:the coming of age[J].Mol Cell,2017,65(1):8-24.
6.Yang Y,Bedford MT.Protein arginine methyltransferases and cancer[J].Nat Rev Cancer,2013,13(1):37-50.
7.Kanda M,Shimizu D,Fujii T,et al.Protein arginine methyltransferase5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer[J].Int J Oncol,2016,49(3):1195-1202.
8.Liu X,Zhang J,Liu L,et al.Protein arginine methyltransferase5-mediated epigenetic silencing of IRX1 contributes to tumorigenicity and metastasis of gastric cancer[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(9 Pt B):2835-2844.
9.许婷,曹仁贤.蛋白质精氨酸甲基转移酶家族与肿瘤的关系[J].现代医药卫生,2015,31(1):67-70.XU Ting,CAO Renxian.Protein arginine methyltransferases and cancer[J].Modern Medicine Health,2015,31(1):67-70.
10.文君,闵雪洁,赵丽,等.蛋白质精氨酸甲基转移酶在肿瘤中的作用及机制研究进展[J].上海交通大学学报(医学版),2017,37(6):842-846.WEN Jun,MIN Xuejie,ZHAO Li,et al.Research progress of e?ect and mechanism of protein arginine methyltransferase in tumors[J].Journal of Shanghai Jiao Tong University.Medical Science,2017,37(6):842-846.