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

  • Published online on: August 4, 2015     https://doi.org/10.3892/ijo.2015.3111
  • Pages: 1545-1553
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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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October-2015
Volume 47 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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