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miR-199a-3p inhibits hepatocyte growth factor/c-Met signaling in renal cancer carcinoma

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Tumor Biology

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that bind protein-coding mRNAs and negatively regulate protein expression by translation repression or mRNA cleavage. Accumulating evidence suggests that miRNAs are involved in cancer development and progression, acting as either tumor suppressors or oncogenes. It has been shown that miR-199a-3p was significantly down-regulated in several types of cancers. However, its role and relevance in renal cell carcinoma (RCC) are still largely unknown. Here, we show that miR-199a-3p is significantly down-regulated in human RCC primary tumors and cell lines compared to their non-tumor counterparts. Moreover, the down-regulation of miR-199a-3p is correlated with the histological grade and TNM (tumor–lymph node–metastasis) stage of RCC. Reintroducing miR-199a-3p in RCC cell lines 769-P and Caki-1 inhibited cell proliferation and caused G1 phase arrest. We found that c-Met was up-regulated in RCC cell lines and its expression could be repressed by miR-199a-3p. Moreover, c-Met was up-regulated in RCC primary tumors and reversely correlated with miR-199a-3p expression in the same paired RCC tissues. Reintroducing miR-199a-3p inhibited c-Met expression and led to attenuated activation of c-Met downstream signaling pathways including STAT3, mTOR and ERK1/2. We found that the concentrations of serum hepatocyte growth factor (HGF), the ligand of c-Met receptor, were significantly elevated in RCC patients compared to healthy persons. In addition, HGF treatment could promote proliferation of RCC cells, and the increased cell proliferation was abrogated by miR-199a-3p. Our findings indicated that miR-199a-3p target HGF/c-Met signaling pathway which is crucial for RCC development and suggest that miR-199a-3p may serve as a potential target miRNA for RCC therapy.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81072097, 81272841), and Basic Research Program of Science and Technology Commission Foundation of Shanghai (10JC1409600).

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Authors and Affiliations

  1. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 168 Pujian Road, Pudong District, Shanghai, 200127, China

    Jiwei Huang, BaiJun Dong, Jin Zhang, Wen Kong, Yonghui Chen, Wei Xue, Dongming Liu & Yiran Huang

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  1. Jiwei Huang
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  2. BaiJun Dong
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  3. Jin Zhang
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Correspondence to Yiran Huang.

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Fig. S1

Ct value of the U6 RNA in 44 paired RCC tumor and matched non-tumor tissues using quantitative RT-PCR assay. Equal amounts of RNA were used for all the samples (JPEG 619 kb)

Fig. S2

Ct value of the U6 RNA in seven paired RCC tumor and matched non-tumor tissues using quantitative RT-PCR assay. Equal amounts of RNA were used for all the samples (JPEG 182 kb)

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Huang, J., Dong, B., Zhang, J. et al. miR-199a-3p inhibits hepatocyte growth factor/c-Met signaling in renal cancer carcinoma. Tumor Biol. 35, 5833–5843 (2014). https://doi.org/10.1007/s13277-014-1774-7

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  • DOI: https://doi.org/10.1007/s13277-014-1774-7

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