Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells

  • Authors:
    • Seung-Ki Min
    • Sung Youn Jung
    • Hyun Ki Kang
    • Sin-A Park
    • Jong Ho Lee
    • Myung-Jin Kim
    • Byung-Moo Min
  • View Affiliations

  • Published online on: September 14, 2017     https://doi.org/10.3892/ijo.2017.4124
  • Pages: 1541-1552
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Abstract

Numerous studies implicate miR-146a as pleiotropic regulator of carcinogenesis; however, its roles in carcinogenesis are not fully understood. A clue from expression analyses of miR-146a-5p in all 13 oral squamous cell carcinoma (OSCC) cell lines examined and in OSCC tissues, whole blood and whole saliva of OSCC patients in vivo revealed that miR‑146a-5p expression was highly upregulated. Particularly, we widened the view of its upregulation in saliva, implicating that high miR-146a-5p expression is not only correlated closely to the development of human oral cancer, but also to a possible candidate as a diagnostic marker of OSCC. Indeed, further examination showed that exogenous miR-146a-5p expression showed pleiotropic effects on cell proliferation and apoptosis which were partially based on the contextual responses of activation of JNK, downstream of TRAF6 that was targeted by miR-146a-5p in normal human keratinocytes and OSCC cell lines. TRAF6 suppression by a TRAF6-specific siRNA resulted in contradictory consequences on cellular processes in normal and OSCC cells. Notably, TRAF6 downregulation by both miR-146a-5p and TRAF6-specific siRNA deactivated JNK in SCC-9, but not in normal human keratinocytes. In support of the proliferation-promoting effect of miR-146a-5p, silencing of endogenous miR-146a-5p significantly reduced proliferation of SCC-9. Together, these results suggest that miR-146a-5p affects proliferation and apoptosis in a cellular context-dependent manner and selectively disarms the TRAF6-mediated branch of the TGF-β signaling in OSCC cell lines by sparing Smad4 involvement.
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November-2017
Volume 51 Issue 5

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

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Spandidos Publications style
Min S, Jung SY, Kang HK, Park S, Lee JH, Kim M and Min B: Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells. Int J Oncol 51: 1541-1552, 2017
APA
Min, S., Jung, S.Y., Kang, H.K., Park, S., Lee, J.H., Kim, M., & Min, B. (2017). Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells. International Journal of Oncology, 51, 1541-1552. https://doi.org/10.3892/ijo.2017.4124
MLA
Min, S., Jung, S. Y., Kang, H. K., Park, S., Lee, J. H., Kim, M., Min, B."Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells". International Journal of Oncology 51.5 (2017): 1541-1552.
Chicago
Min, S., Jung, S. Y., Kang, H. K., Park, S., Lee, J. H., Kim, M., Min, B."Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells". International Journal of Oncology 51, no. 5 (2017): 1541-1552. https://doi.org/10.3892/ijo.2017.4124