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Selective killing of lung cancer cells by miRNA-506 molecule through inhibiting NF-κB p65 to evoke reactive oxygen species generation and p53 activation

Oncogene volume 34, pages 691–703 (2015)Cite this article

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Abstract

The tumor suppressor p53, nuclear factor-κB (NF-κB) and reactive oxygen species (ROS) have crucial roles in tumorigenesis, although the mechanisms of cross talk between these factors remain largely unknown. Here we report that miR-506 upregulation occurs in 83% of lung cancer patients (156 cases), and its expression highly correlates with ROS. Ectopic expression of miR-506 inhibits NF-κB p65 expression, induces ROS accumulation and then activates p53 to suppress lung cancer cell viability, but not in normal cells. Interestingly, p53 promotes miR-506 expression level, indicating that miR-506 mediates cross talk between p53, NF-κB p65 and ROS. Furthermore, we demonstrated that miR-506 mimics inhibited tumorigenesis in vivo, implicating that miR-506 might be a potential therapeutic molecule for selective killing of lung cancer cells.

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Acknowledgements

We would like to thank Professor Craig Mello for valuable advice throughout this research, Professor Miguel Esteban for manuscripts revision and renal cell line RCC4, Professor Duanqing Pei for the lung cancer cell line 95D. This research was supported by Introduced Innovative R&D Team Program of Guangdong Province (no. 201001Y0104789252), 863 Program of China (no. 2012AA022501), Strategic Emerging Industry Key Technology Project of Guangdong Province (no. 2012A080800006), the National Natural Science Foundation of China (nos. 30870535 and 90913017), the "Hundred Talents Plan" of Guangzhou Municipality and Combination Project of Guangdong Province and the Ministry of Education (no. 2011B090400478).

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  1. M Yin and X Ren: These two authors contributed equally to this work.

Authors and Affiliations

  1. The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

    M Yin, X Ren, G Wang, X Bao, P Liang, Z Wang & B Zhang

  2. School of Life Science, University of Science and Technology of China, Hefei, China

    M Yin, X Ren, X He & B Zhang

  3. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China

    X Zhang, H Tang & J He

  4. Guangzhou RiboBio Co., Ltd, Guangzhou, China

    Y Luo, K Huang & S Feng

  5. University of Chinese Academy of Sciences, Beijing, China

    K Huang & P Liang

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Yin, M., Ren, X., Zhang, X. et al. Selective killing of lung cancer cells by miRNA-506 molecule through inhibiting NF-κB p65 to evoke reactive oxygen species generation and p53 activation. Oncogene 34, 691–703 (2015). https://doi.org/10.1038/onc.2013.597

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