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MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

Oncogene volume 31, pages 4509–4516 (2012)Cite this article

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Abstract

Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3′-untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

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Acknowledgements

We are most grateful for Dr T Didier's gifts of the pWPXL, psPAX2 and pMD2.G lenti-virus plasmids.

Author contributions: BZ, LL, YS, and XH designed the experiments, interpreted the data and wrote the manuscript. BZ, LL, SH, LL, DJ and QT performed experiments. RZ and QW conducted the animal experiments. CW, ZL, YZ, XC and CD collected the human samples and clinical data.

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  1. B Zheng and L Liang: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Gastric Cancer and Soft Tissue Sarcomas, Fudan University Shanghai Cancer Center, Shanghai, China

    B Zheng, Q Wang, C Wang, Z Long, Y Zhou, X Cao, C Du, Y Shi & X He

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    B Zheng, Q Wang, C Wang, Z Long, Y Zhou, X Cao, C Du, Y Shi & X He

  3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    L Liang, S Huang, R Zha, L Liu, D Jia, Q Tian & X He

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  1. B Zheng
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Correspondence to Y Shi or X He.

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Zheng, B., Liang, L., Huang, S. et al. MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers. Oncogene 31, 4509–4516 (2012). https://doi.org/10.1038/onc.2011.581

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  • DOI: https://doi.org/10.1038/onc.2011.581

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