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Article

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 / Copyright

    Affiliations: Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-Do 10408, Republic of Korea, Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea, Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea
  • Pages: 1541-1552
    |
    Published online on: September 14, 2017
       https://doi.org/10.3892/ijo.2017.4124
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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