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miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma

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Abstract

Purpose

Abnormal expression of miRNAs is closely related to a variety of human cancers. The purpose of this study is to identify new tumor suppressor miRNA and elucidate its physiological function and mechanism in renal cell carcinoma (RCC).

Methods

The expression of miR-145 in 45 RCC and adjacent normal tissues was performed by quantitative RT-PCR. Cell proliferation, migration, invasion, apoptosis and cycle assays were carried out for functional analysis after miR-145 transfection. Two target genes of miR-145 were identified by luciferase reporter assay. The altered expression of 84 epithelial to mesenchymal transition (EMT)-related genes after miR-145 transfection was detected by RT2 Profiler EMT PCR array.

Results

The expression of miR-145 was downregulated in RCC compared to their normal adjacent tissues. Restoring miR-145 expression in RCC cell lines dramatically suppressed cell proliferation, migration and invasion, and induced cell apoptosis and G2-phase arrest. We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT.

Conclusions

These findings demonstrate that miR-145 functions as tumor suppressor in RCC, suggesting that miR-145 may be a potential therapeutic target for RCC.

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Acknowledgments

This project was supported by Science and Technology Planning Project of Shenzhen in China (No. 201102006) and Science and Technology Planning Project of Guangdong Province, China (No. 2011B031800381).

Conflict of interest

We declare that we have no conflict of interest in relation to this article.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518036, China

    Ruijing Lu, Xiaoqing Li, Qingna Zhai, Chunjuan Zhao & Liping Nie

  2. Shantou University Medical College, Shantou, 515041, China

    Ruijing Lu, Ziliang Ji, Xiaoqing Li, Qingna Zhai & Chunjuan Zhao

  3. Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Shenzhen PKU-HKUST Medical Center, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen, 518036, China

    Ziliang Ji, Zhimao Jiang & Shiqiang Zhang

  4. Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, 518036, China

    Zhendong Yu

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  1. Ruijing Lu
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  2. Ziliang Ji
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  3. Xiaoqing Li
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  4. Qingna Zhai
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  8. Liping Nie
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  9. Zhendong Yu
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Corresponding author

Correspondence to Zhendong Yu.

Additional information

Ruijing Lu and Ziliang Ji have contributed equally to this work.

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Lu, R., Ji, Z., Li, X. et al. miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol 140, 387–397 (2014). https://doi.org/10.1007/s00432-013-1577-z

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  • DOI: https://doi.org/10.1007/s00432-013-1577-z

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