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Article

MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2

  • Authors:
    • Dong Ho Park
    • Hyo Sung Jeon
    • Soo Young Lee
    • Yi Young Choi
    • Hae Woo Lee
    • Seongkyu Yoon
    • Jae Chel Lee
    • Yoo Sang Yoon
    • Dae Sung Kim
    • Moon Jun Na
    • Sun Jung Kwon
    • Dong Sun Kim
    • Jaeku Kang
    • Jae Yong Park
    • Ji Woong Son
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology and Pain Medicine, Konyang University Hospital, Daejeon, Republic of Korea, The Molecular Diagnostics and Imaging Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Myunggok Research Institute for Medical Science, Konyang University, Daejeon, Republic of Korea, Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Clinical Drug Manufacturing Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea, Department of Chemical Engineering, University of Massachusetts Lowell, MA, USA, Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea, Department of Thoracic Surgery, Konyang University Hospital, Daejeon, Republic of Korea, Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea, Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea, Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea
  • Pages: 1545-1553
    |
    Published online on: August 4, 2015
       https://doi.org/10.3892/ijo.2015.3111
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Abstract

During cancer progression, some tumor cells show changes in their plasticity by morphological and phenotypical conversions, as an expression of mesenchymal markers and loss of epithelial markers, collectively referred to as epithelial-mesenchymal transition (EMT). EMT has been increasingly recognized as a critical phenomenon in lung cancer progression. The goal of this study was to identify microRNAs involved in lung cancer progression. A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in mesenchymal-like lung cancer cells. The role of miR‑146a in lung cancer progression was measured by invasion and migration assays in vitro. Bioinformatics and luciferase report assays were used to identify the target of miR‑146a. The expression of miR‑146a was reduced in mesenchymal-like lung cancer cell lines. The overexpression of miR‑146a induced a marked reduction of the mesenchymal marker and increase the epithelial marker in lung cancer cell lines. Moreover, the overexpression of miR‑146a suppressed lung cancer cell migration and invasion. Co-treatment with miR‑146a and gefitinib treatment showed a significant reduction of invasion in the resistant lung cancer cells induced by EMT. The expression of miR‑146a was downregulated in advanced lung cancer tissues. Insulin receptor substrate 2 (IRS2), an adaptor protein that modulates normal growth, metabolism, survival, and differentiation, was identified as a target of miR‑146a. miR‑146a regulated the expression of IRS2 at the mRNA and protein levels. These data demonstrate for the first time that miR‑146a suppresses lung cancer progression by repressing IRS2 expression. This provides new insight into the post-transcriptional regulation of lung cancer progression by miRNAs, a potential approach for the treatment of lung cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Park DH, Jeon HS, Lee SY, Choi YY, Lee HW, Yoon S, Lee JC, Yoon YS, Kim DS, Na MJ, Na MJ, et al: MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. Int J Oncol 47: 1545-1553, 2015.
APA
Park, D.H., Jeon, H.S., Lee, S.Y., Choi, Y.Y., Lee, H.W., Yoon, S. ... Son, J.W. (2015). MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. International Journal of Oncology, 47, 1545-1553. https://doi.org/10.3892/ijo.2015.3111
MLA
Park, D. H., Jeon, H. S., Lee, S. Y., Choi, Y. Y., Lee, H. W., Yoon, S., Lee, J. C., Yoon, Y. S., Kim, D. S., Na, M. J., Kwon, S. J., Kim, D. S., Kang, J., Park, J. Y., Son, J. W."MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2". International Journal of Oncology 47.4 (2015): 1545-1553.
Chicago
Park, D. H., Jeon, H. S., Lee, S. Y., Choi, Y. Y., Lee, H. W., Yoon, S., Lee, J. C., Yoon, Y. S., Kim, D. S., Na, M. J., Kwon, S. J., Kim, D. S., Kang, J., Park, J. Y., Son, J. W."MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2". International Journal of Oncology 47, no. 4 (2015): 1545-1553. https://doi.org/10.3892/ijo.2015.3111
Copy and paste a formatted citation
x
Spandidos Publications style
Park DH, Jeon HS, Lee SY, Choi YY, Lee HW, Yoon S, Lee JC, Yoon YS, Kim DS, Na MJ, Na MJ, et al: MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. Int J Oncol 47: 1545-1553, 2015.
APA
Park, D.H., Jeon, H.S., Lee, S.Y., Choi, Y.Y., Lee, H.W., Yoon, S. ... Son, J.W. (2015). MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2. International Journal of Oncology, 47, 1545-1553. https://doi.org/10.3892/ijo.2015.3111
MLA
Park, D. H., Jeon, H. S., Lee, S. Y., Choi, Y. Y., Lee, H. W., Yoon, S., Lee, J. C., Yoon, Y. S., Kim, D. S., Na, M. J., Kwon, S. J., Kim, D. S., Kang, J., Park, J. Y., Son, J. W."MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2". International Journal of Oncology 47.4 (2015): 1545-1553.
Chicago
Park, D. H., Jeon, H. S., Lee, S. Y., Choi, Y. Y., Lee, H. W., Yoon, S., Lee, J. C., Yoon, Y. S., Kim, D. S., Na, M. J., Kwon, S. J., Kim, D. S., Kang, J., Park, J. Y., Son, J. W."MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2". International Journal of Oncology 47, no. 4 (2015): 1545-1553. https://doi.org/10.3892/ijo.2015.3111
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