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c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT

Oncogene volume 34, pages 2072–2082 (2015)Cite this article

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Abstract

The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan–Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.

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Acknowledgements

This work was jointly supported by grants from the National Health Research Institute (NHRI96-TD-G-111-006; NHRI97-TD-G-111-006) and the National Science Council(100-2314-B-038-043-MY3) of Taiwan, ROC.

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Authors and Affiliations

  1. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    D-W Wu, N-Y Hsu, Y-W Cheng & H Lee

  2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Y-C Wang

  3. Department of Chest Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    Y-C Wang

  4. Department of Thoracic Surgery, Taichung Veteran General Hospital, Taichung, Taiwan

    M-C Lee

  5. Department of Surgery, China Medical University Hospital, Taichung, Taiwan

    C-Y Chen

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Correspondence to H Lee.

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Wu, DW., Hsu, NY., Wang, YC. et al. c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT. Oncogene 34, 2072–2082 (2015). https://doi.org/10.1038/onc.2014.152

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