Dicer suppresses MMP-2-mediated invasion and VEGFA-induced angiogenesis and serves as a promising prognostic biomarker in human clear cell renal cell carcinoma.
Dicer suppresses MMP-2-mediated invasion and VEGFA-induced angiogenesis and serves as a promising prognostic biomarker in human clear cell renal cell carcinoma.
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Dicer 抑制 MMP-2 介导的侵袭和 VEGFA 诱导的血管生成，并可作为人透明细胞肾细胞癌的有前途的预后生物标志物
DOI：
10.18632/oncotarget.12520
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发表时间：
2016-12-20
期刊：
影响因子：
--
通讯作者：
Zheng JN
中科院分区：
文献类型：
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作者：
Chen YS;Meng F;Li HL;Liu QH;Hou PF;Bai J;Zheng JN
Dicer是microRNA加工机制的关键组成部分，据报道在不同类型的癌症中发挥不同的预后价值和生物学作用。在此，我们研究了Dicer在肾透明细胞癌（ccRCC）中的功能和预后价值。使用回顾性ccRCC患者队列与组织芯片（TMA），我们证明了与肾非肿瘤组织相比，在ccRCC中Dicer表达显著下调，并且与pN状态（P = 0.005），pM状态（P = 0.009）和TNM分期（P =0.013）呈负相关。多因素考克斯比例风险回归分析显示，Dicer阳性表达是影响ccRCC患者预后的独立有利因素（风险比（HR）= 0.709，5年总生存率P = 0.025;疾病特异性生存率HR = 0.655，P = 0.008）。Dicer通过抑制MMP-2和VEGFA的表达，降低了细胞的迁移、侵袭和血管生成能力。体内肿瘤转移模型显示，Dicer敲低组的肺转移结节比对照组多得多，这是由于MMP-2表达增加。我们的研究结果表明，Dicer抑制ccRCC转移，并可能成为ccRCC患者有前途的预后生物标志物。
Dicer, a key component of the microRNA processing machinery, has been reported to exert discrepant prognostic values and biological roles in different types of cancers. Here, we investigated the function and prognostic value of Dicer in clear cell renal cell carcinoma (ccRCC). Using the retrospective ccRCC patients’ cohorts with tissue microarray (TMA), we demonstrated that Dicer expression was significantly down-regulated in ccRCC compared with renal non-tumor tissues, and negatively associated with pN status (P = 0.005), pM status (P = 0.009) and TNM stage (P =0.013). Multivariate Cox proportional hazards regression analyses showed that positive Dicer expression was an independent favorable factor for prognosis of ccRCC patients (hazard ratio (HR) = 0.709, P = 0.025 for 5-year overall survival; HR = 0.655, P = 0.008 for disease specific survival). Moreover, we found that Dicer decreased the abilities of cell migration, invasion and angiogenesis through suppressing MMP-2 and VEGFA expression. Tumor metastasis model in vivo showed much more metastatic nodules of lung in the Dicer knockdown group than the control group via increased MMP-2 expression. Our findings imply that Dicer inhibits ccRCC metastasis and may serve as promising prognostic biomarkers for ccRCC patients.