目的:探讨Dicer在肾透明细胞癌发生及转移中的作用。方法:选取正常肾小管上皮细胞株HKC、非转移性肾透明细胞癌细胞株769P、转移性肾透明细胞癌细胞株Caki-1以及36例肾透明细胞癌手术标本(其中11例已发生远处转移)和相应癌旁正常肾组织,应用实时定量PCR和Western blot方法检测Dicer在肾透明细胞癌细胞株和组织中mRNA和蛋白的表达情况,并分析Dicer的mRNA水平与临床病理资料的关系。结果:和正常肾小管上皮细胞株HKC相比;Dicer的mRNA水平在肾透明细胞癌细胞株769-P和Caki-1中均降低(P〈0.001),而转移性肾透明细胞癌细胞株Caki-1比非转移性肾透明细胞癌细胞株769-P表达水平更低(P〈0.001);和癌旁正常肾组织相比,Dicer的mRNA水平在‘肾透明细胞癌手术标本中明显降低(P〈0.001),且已发生远处转移的。肾癌标本比未发生远处转移的肾癌标本表达水平更低(P=0.04);Dicer在细胞株和组织中的蛋白水平的变化与mRNA水平的变化一致(P〈0.001);Dicer的mRNA水平在不同年龄、性别、组织学分级、肿瘤大小及T分期组间无统计学差异(P〉0.05)。结论:Dicer表达降低可能在。肾透明细胞癌的肿瘤发生中发挥作用,且其表达的进一步下降可能与肾透明细胞癌的远处转移有关。
Objective:To explore the role of Dicer in tumorigenesis and metastasis of clear cell renal cell carci-noma (ccRCC). Method:The expression of Dicer in mRNA and protein levels were detected in human kidney tubule epithelial cell line HKC, non-metastatic ccRCC cell line 769-P, metastatic ccRCC cell line Caki-1, and 36 cases of ccRCC surgical specimens(including 11 cases with distant metastasis)and their corresponding adjacent normal renal tissues by real-time PCR and Western blot respectively, analyzing the relationship between the mRNA levels of Dicer and clinicopathological variables. Result:Compared to human kidney tubule epithelial cell line HKC, the mR- NA levels of Dicer were significantly down regulated in ccRCC cell lines of 769-P and Caki 1 ( P 〈0. 001), with the metastatic ccRCC cell line Caki-1 even lower( P 〈0. 001). Meanwhile, the mRNA levels of Dicer were signifi- cantly down-regulated in ccRCC surgical specimens compared to adjacent normal renal tissues ( P〈0.001), with the metastatic ones further reduced ( P =0. 04). The alteration of the protein levels in ccRCC cell lines and tissues were consistent with that of the mRNA levels ( P〈0. 001). The mRNA levels of Dicer were not significantly dif-ferent among different groups, in terms of age, sex, histological staging, tumor size and T staging ( P〉0.05).Conclusion: Reduced expression of Dicer may play a role in the tumorigenesis of ccRCC, and expression of a furtherdecline may relate to distant metastasis of ccRCC.