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miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin

Oncogene volume 36, pages 275–285 (2017)Cite this article

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Abstract

miR-374a has been reported to function as an oncogene during tumor pathogenesis. In this study, miR-374a is observed to reduce nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, metastasis and cisplatin (DDP) resistance in vitro and in vivo. Mechanistic analyses indicate that miR-374a directly targets CCND1 to inactivate pPI3K/pAKT/c-JUN forming a negative feedback loop, as well as suppressing downstream signals related to cell cycle progression and epithelial−mesenchymal transition (EMT). Interestingly, we also observed that miR-374a direct targeting of CCND1 is modulated by tumor suppressor PDCD4 via suppressing pPI3K/pAKT/c-JUN signaling. In clinical specimens, miR-374a was positively and negatively correlated with expression of PDCD4 and CCND1, respectively. Our studies are the first to demonstrate that the miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop induced by PDCD4 supresses NPC cell growth, metastasis and chemotherapy resistance.

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Acknowledgements

This study was supported by National Nature Science Fund of China (No. 81372184 and No. 81401906) (http://www.nsfc.gov.cn), the Outstanding Young Teacher Training Project of Colleges and Universities in Guangdong Province (No. Yq2013136), Guangdong Province Education Foundation (No. 2014KTSCX107), and Yangcheng Scholar Research Projects from Universities of Guangzhou (No. 12A011D). We are also grateful to Dr Douglas E Linn (Brigham & Women’s Hospital, Boston, MA, USA) for critical reading of the manuscript.

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Author notes

  1. Y Zhen, W Fang, M Zhao and R Luo: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Center, TCM-Integrated Hospital, Southern Medical University, Guangzhou, China

    Y Zhen, W Fang & R Luo

  2. Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, PR, China

    Y Zhen

  3. Cancer Research Institute, Southern Medical University, Guangzhou, PR, China

    Y Zhen, W Fang, M Zhao, Y Liu, Q Fu, Y Chen, C Cheng & Z Liu

  4. Department of Pathology, School of Basic Medicine, Guangzhou Medical University, Guangzhou, PR, China

    Y Zhang & Z Liu

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  1. Y Zhen
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Correspondence to W Fang or Z Liu.

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Zhen, Y., Fang, W., Zhao, M. et al. miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin. Oncogene 36, 275–285 (2017). https://doi.org/10.1038/onc.2016.201

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