MicroRNA-145在肾癌中的临床意义及其分子机制探讨

目的:探讨miRNA-145在肾癌中的临床意义及其分子机制。方法:通过实时定量PCR检测和比较16例肾癌患者的肿瘤组织及癌旁正常肾组织中miRNA-145的表达,并分析miRNA-145的表达水平与肾癌患者病理特征及临床分级的相关性。进一步采用实时定量PCR检测和比较肾癌细胞株786-O、769P及正常肾细胞株HK2中miRNA-145表达量,通过转染miRNA-145 mimics和阴性对照miRNA至769P、786-O肾癌细胞株后观察癌基因(bcl-2、e2f3、cdk6、ccnd1)mRNA的表达。结果:肾癌组织中miRNA-145的表达显著低于癌旁正常肾组织(P0.05),且与肾癌的直径、病理核分级及临床分级呈显著负相关(P0.05)。肾癌细胞株769P、786-O中miRNA-145的表达显著低于正常HK-2肾细胞(P0.05),而转染miRNA-145 mimics的769P、786-O细胞中多个癌基因(bcl-2、e2f3、cdk6、ccnd1)的mRNA表达均较阴性对照组显著降低(P0.05)。结论:MiRNA-145在肾癌中呈低表达,可能通过调控多个癌基因的表达在肾癌的发生发展过程中发挥重要的作用。

Clinical Significance and Molecular Mechanismof MicroRNA-145 in Renal Cell Carcinoma

Objective:To investigate the clinical significance and molecular mechanism of miRNA-145 in renal cell carcinoma (RCC).Methods:Quantitative real time PCR was used to examine and compare the miRNA-145 expression in 16 cases of RCC and adjacent normal renal tissues, and further in RCC cell lines 786-O, 769P and normal HK2 cell lines. The correlation of miRNA-145 expression with clinicopathological charateristics and clinical grading were analyzed. After being transfected with the miRNA-145 mimics, the expression levels of multiple oncogenes (bcl-2, e2f3, cdk6, ccnd1) in RCC cell lines 786-O, 769P and normal HK2 cell line were examined by QRT-PCR.Results:The miRNA-145 expression was downregulated in RCC tissue in comparison with that in the normal renal tissue (P<0.05), which was negatively correlated with the diameter, pathological nuclear grading and clinical grading of RCC(P<0.05). The miRNA-145 expression was significantly lower in RCC cell lines 786-O, 769P than that in the normal HK2 cell line (P<0.05). The overexpression of miRNA-145 in 786-O, 769P cells significantly decreased the mRNA expression of multiple oncogenes (bcl-2, e2f3, cdk6, ccnd1) (P<0.05).Conclusion:MiRNA-145 was downregulated in RCC, and may play an important role in the renal carcinogenesis through regulating multiple oncogenes.