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miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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

The 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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (NSFC) (Grant Nos. 30872924, 81072095 & 81372760), Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223), the National High Technology Research and Development Program of China (863 Program) (2012AA021101) to Xiaoping Zhang and the NSFC (Grant Nos. 31070142 & 81272560) to Hongmei Yang.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People’s Republic of China

    Xuanyu Chen, Anming Ruan, Xuegang Wang, Weiwei Han, Rong Wang, Ning Lou, Hailong Ruan, Bin Qiu & Xiaoping Zhang

  2. Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China

    Hongmei Yang

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  1. Xuanyu Chen
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  2. Anming Ruan
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  3. Xuegang Wang
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Correspondence to Xiaoping Zhang.

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Supplemental Information Fig. S1 No significant correlation between miR-129-3p and tumor size, stage or grade was observed in ccRCC (PDF 128 kb)

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Chen, X., Ruan, A., Wang, X. et al. miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes. J Cancer Res Clin Oncol 140, 1295–1304 (2014). https://doi.org/10.1007/s00432-014-1690-7

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