Musashi-1在前列腺癌中的表达及其临床意义

Expression and clinical significance of musashi RNA-binding protein 1 in prostate cancer

目的探讨RNA结合蛋白Musashi-1(MSI1)在前列腺癌(PCa)中的表达及其调控功能。方法基于肿瘤基因组图谱(TCGA)数据库对目的基因MSI1进行差异分析、生存分析和临床相关性分析。通过在DU145细胞中敲低目的基因, 探究MSI1其对前列腺癌细胞DU145增殖、迁移和侵袭能力的影响, 组间比较采用独立样本t检验。结果 MSI1在前列腺癌中表达水平明显高于正常前列腺组织, 差异有统计学意义(7.75±1.01比4.56±0.54, t= 4.82, P<0.01)。且生存分析结果显示, 低表达MSI1组的无病生存期明显长于高表达组[风险比(HR):1.71(1.15~2.53), P<0.01]。T1+T2期MSI1表达水平和T3+T4期表达水平无统计学意义(t=0.38, P>0.05)。MSI表达水平[HR:1.47(1.02~2.10), P<0.05]、T分期[HR:1.93(1.02~3.60), P<0.05]及Gleason评分[HR:3.17(1.59~6.30), P<0.01]可作为前列腺癌的预后因素。细胞计数试剂盒(CCK-8)结果, 第4天Ctrl DU145细胞在波长450 nm吸光度(A)值为0.929±0.085, 而shMSI1#1和shMSI1#2 DU145实验组第4天A值分别为0.687±0.005和0.711±0.018, 与对照组比较差异有统计学意义(t=42.21、44.19, P<0.01)。DU145中ctrl组伤口愈合面积显著高于si-MSI1#1和si-MSI1#2组, 组间比较差异有统计学意义(P<0.01)。同时前列腺癌细胞迁移侵袭实验发现, ctrl组及si-MSI1#1和si-MSI1#2组PC3迁移细胞分别为790.9±80.7、403.3±49.9和504.6±117.3, 组间比较差异有统计学意义(t=21.80、13.55, P<0.01)。结论 MSI1在前列腺癌组织中高表达且与前列腺癌患者的不良预后明显相关。抑制MSI1可有效抑制前列腺癌细胞的增殖、侵袭能力。

Objective To investigate the expression and regulatory function of RNA binding pro-tein musashi RNA-binding protein 1(MSI1)in prostate cancer(PCa).Methods The differential analy-sis,survival analysis and clinical correlation analysis of MSIl gene were performed based on the cancer ge-nome atlas(TCGA)database.By knocking down the target gene in DU145 cells,the effect of MSIl on the proliferation,migration and invasion of prostate cancer cells DU145 was explored,and the t test was used for comparison between groups.The target gene MSIl was knocked down at two levels,and its effects on the viability,proliferation and invasion of prostate cancer cells were investigated.Results The expression level of MSIl in prostate cancer was significantly higher than that in normal prostate tissue,and the differ-ence was statistically significant(7.75±1.01 vs.4.56±0.54,t=4.82,P<0.01).The results of sur-vival analysis showed that the disease-free survival of the low-expression MSIl group was significantly longer than that of the high-expression group[hazard ratio(HR)=1.71(1.15-2.53),P<0.01].There was no statistically significant difference between the expression levels of MSII in T1+T2 stage and T3+T4 stage(t=0.38,P>0.05).MSI expression level[HR:1.47(1.02-2.10),P<0.05],T stage[HR:1.93(1.02-3.60),P<0.05]and Gleason score[HR:3.17(1.59-6.30),P<0.01]could be used as prognos-tic factors for prostate cancer.Compared with normal prostate samples,the expression level of MSIl in prima-ry prostate cancer samples was significantly increased(P<0.01),and the progression-free survival time of patients with low MSII expression was significantly longer than that of patients with high MSIl expression(P<0.05).There was no significant difference in the expression level of MSIl with T stage,N stage and Gl-eason score in prostate cancer patients(P>0.05),while T stage and Gleason score including MSI1 could be used as risk factors for prostate cancer(P<0.05).After MSIl gene knockdown,the viability,proliferation and invasion ability of prostate cancer cells were measured.cell counting kit-8(CCK-8)results:on day 4,the absorbance value Optical density of Ctrl DU145 cells at a wavelength of 450 nm was 0.929±0.085,while the absorbance(A)values of shMSIl#1 and shMSI1#2 DU145 experimental groups on day 4 were 0.687±0.005 and 0.711±0.018 respectively,the different between them was significant(t=42.21,44.19,P<0.01).In DU145,the wound healing area of the ctrl group was significantly higher than that of the si-MSIl#1 and si-MSIl#2 groups,and the difference between the groups was statistically significant(P<0.01).Furthermore,the number of PC3 migrated cells in the ctrl group,si-MSI1#1 and si-MSIl#2 groups were 790.9±80.7,403.3±49.9 and 504.6±117.3 respectively.The difference is statistically significant(t=21.80,13.55,P<0.01).Conclusion The expression of MSI1 is high in prostate cancer tissues and is related to the poor prognosis of prostate cancer patients.MSIl gene may play an important role in the proliferation and invasion of prostate cancer.MSI1 is expected to be a potential biomarker for the diagnosis of prostate cancer and a potential target for drug treatment and prognosis prediction.