miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes
miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes
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miR-129-3p 作为肾细胞癌的诊断和预后生物标志物，通过下调多个转移相关基因来减弱细胞迁移和侵袭
DOI：
10.1007/s00432-014-1690-7
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发表时间：
2014-08-01
影响因子：
3.6
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Chen, Xuanyu;Ruan, Anming;Zhang, Xiaoping
目的miRNA表达下调是肾细胞癌(RCC)的新特征。最近，众所周知miR-129-2经常被DNA甲基化降低，并且在各种肿瘤中具有抗肿瘤作用，但到目前为止在肾癌中还没有。方法采用实时定量逆转录聚合酶链式反应技术，检测69例不同类型肾肿瘤、正常肾组织和肾透明细胞癌(CcRCC)中miR-129-2成熟产物miR-129-3p和miR-129-5p的表达。通过功能分析评价它们在肾癌细胞中的作用。结果miR-129-3p在人肾细胞癌和嫌色肾细胞癌中广泛表达，而miR-129-5p不表达。MIR-129-3P对癌组织与正常组织的鉴别准确率为73.5%。MiR-129-3p在恶性和良性肾肿瘤中的相对表达差异有统计学意义。重要的是，低miR-129-3p水平与较短的无病生存期和总生存期相关。异位表达miR-129-3p可显著降低肾癌细胞的迁移和侵袭能力，但对细胞活力和细胞周期分布无明显影响。结论miR-129-3p可作为鉴别肾细胞癌与良性肿瘤及正常组织的诊断标志物，并可作为判断肾细胞癌预后的独立标志物。MIR-129-3P可能通过调节多个靶点发挥抗转移作用。
Purpose Downregulation of miRNA expression has been identified as a novel feature of renal cell carcinoma (RCC). Recently, miR-129-2 is well known to be frequently reduced by DNA methylation and has anti-tumor effects in various tumors but so far not in RCC. The aim of this study was to investigate the clinical significance and the role of it in RCC.Methods T he expression levels of miR-129-3p and miR-129-5p, two mature products of miR-129-2, were determined by real-time quantitative reverse transcription PCR in 69 cases of paired different kidney tumors and normal tissues and clear cell RCC (ccRCC) cell lines. The roles of them in RCC cells were assessed by functional analyses. Protein expression was detected by Western blot.Results miR-129-3p, but not miR-129-5p, was widely attenuated in human ccRCC, and chromophobe RCC. miR-129-3p could yield 73.5 % accuracy in discriminating ccRCCs from normal tissues. The relative miR-129-3p expression significantly differed between malignant and benign kidney tumors. Importantly, low miR-129-3p levels were associated with short disease-free and overall survival. Ectopic expression of miR-129-3p robustly impaired RCC cell migratory and invasive properties, but had no impact on cell viability and cell cycle distribution. Finally, miR-129-3p decreased multiple metastasis-related genes in RCC cells, including SOX4, phosphorylation of focal adhesion kinase and MMP-2/9 expression.Conclusions miR-129-3p may act as a promising diagnostic biomarker for discriminating ccRCC from benign tumors and normal tissues and an independent prognostic biomarker in ccRCC. miR-129-3p may exert its anti-metastatic function through modulating multiple targets.