Machackova Tana, Mlcochova Hana, Stanik Michal, Dolezel Jan, Fedorko Michal, Pacik Dalibor, Poprach Alexandr, Svoboda Marek, Slaby Ondrej
Central European Institute of Technology (CEITEC), Masaryk University, University Campus Bohunice, Building A35, Room 217, Kamenice 5, 625 00, Brno, Czech Republic.
Department of Urologic Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Tumour Biol. 2016 Nov;37(11):14653-14658. doi: 10.1007/s13277-016-5310-9. Epub 2016 Sep 12.
MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-β treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-β-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.
微小RNA（miRNA）已被证明在包括肾细胞癌（RCC）在内的多种癌症中是重要的癌基因和肿瘤抑制因子。在我们的研究中，我们评估了miRNA - 429作为172例透明细胞RCC患者潜在的诊断/预后生物标志物，并在体外作为上皮 - 间质转化（EMT）的潜在调节因子。我们证明miR - 429在肿瘤组织样本中表达下调（P < 0.0001），并且与癌症转移（P < 0.0001）、较短的无病生存期（P = 0.0105）和总生存期（P = 0.0020）显著相关。此外，与经TGF - β处理的对照相比，在786 - 0 RCC细胞中异位表达miR - 429后再进行TGF - β处理，导致E - 钙黏蛋白表达水平增加（P < 0.0001）并抑制细胞迁移（P < 0.0001）。综上所述，我们的研究结果表明miR - 429可能是RCC患者有前景的诊断和预后生物标志物。我们进一步表明，miR - 429有能力抑制经历EMT的RCC细胞中E - 钙黏蛋白的丢失，从而减弱其运动性。
