Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma

  • Authors:
    • Hiroko Mataki
    • Naohiko Seki
    • Takeshi Chiyomaru
    • Hideki Enokida
    • Yusuke Goto
    • Tomohiro Kumamoto
    • Kentaro Machida
    • Keiko Mizuno
    • Masayuki Nakagawa
    • Hiromasa Inoue
  • View Affiliations

  • Published online on: December 18, 2014     https://doi.org/10.3892/ijo.2014.2802
  • Pages: 1039-1050
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Abstract

Expression of the oncogene hepatocyte growth factor receptor (MET) and phosphorylation of the MET protein have been associated with both primary and acquired resistance to tyrosine kinase inhibitors (TKIs) used in therapy targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancers (NSCLCs). Therefore, simultaneous inhibition of both of these receptor tyrosine kinases (RTKs) should improve disease treatment. Our previous study of microRNA (miRNA) expression signatures of lung squamous cell carcinoma (lung-SCC) revealed that microRNA-206 (miR‑206) was significantly reduced in lung-SCC tissues, suggesting that miR‑206 functions as a tumor suppressor in the disease. Furthermore, putative miR‑206 binding sites were annotated in the 3'-UTRs of MET and EGFR RTKs in miRNA databases. The aim of the study was to investigate the functional significance of miR‑206 in lung-SCC and to confirm the inhibition of both MET and EGFR oncogenic signaling by expression of miR‑206 in cancer cells. We found that restoration of mature miR‑206 inhibited cancer cell proliferation, migration, and invasion in EBC-1 cells through downregulation of both mRNA and protein levels of MET and EGFR. Interestingly, phosphorylation of ERK1/2 and AKT signaling were inhibited by restoration of miR‑206 in cancer cells. Overexpression of MET and EGFR were observed in clinical specimens of lung-SCC. Tumor-suppressive miR‑206 inhibited dual signaling networks activated by MET and EGFR, and these findings will provide new insights into the novel molecular mechanisms of lung-SCC oncogenesis and new therapeutic approaches for the treatment of this disease.
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March-2015
Volume 46 Issue 3

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

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Spandidos Publications style
Mataki H, Seki N, Chiyomaru T, Enokida H, Goto Y, Kumamoto T, Machida K, Mizuno K, Nakagawa M, Inoue H, Inoue H, et al: Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma. Int J Oncol 46: 1039-1050, 2015.
APA
Mataki, H., Seki, N., Chiyomaru, T., Enokida, H., Goto, Y., Kumamoto, T. ... Inoue, H. (2015). Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma. International Journal of Oncology, 46, 1039-1050. https://doi.org/10.3892/ijo.2014.2802
MLA
Mataki, H., Seki, N., Chiyomaru, T., Enokida, H., Goto, Y., Kumamoto, T., Machida, K., Mizuno, K., Nakagawa, M., Inoue, H."Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma". International Journal of Oncology 46.3 (2015): 1039-1050.
Chicago
Mataki, H., Seki, N., Chiyomaru, T., Enokida, H., Goto, Y., Kumamoto, T., Machida, K., Mizuno, K., Nakagawa, M., Inoue, H."Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma". International Journal of Oncology 46, no. 3 (2015): 1039-1050. https://doi.org/10.3892/ijo.2014.2802