Dysregulation of RUNX2/activin-A axis upon miR-376c downregulation promotes lymph node metastasis in head and neck squamous cell carcinoma

Wei Min Chang, Yuan Feng Lin, Chia Yi Su, Hsuan Yu Peng, Yu Chan Chang, Tsung Ching Lai, Guan Hsun Wu, Yuan Ming Hsu, Li Hsing Chi, Jenn Ren Hsiao, Chi Long Chen, Jang Yang Chang, Yi Shing Shieh, Michael Hsiao, Shine Gwo Shiah

研究成果: 雜誌貢獻文章

17 引文 斯高帕斯(Scopus)

摘要

Epigenetic correlates of the head and neck cancer may illuminate its pathogenic roots. Through a gene set enrichment analysis, we found that the oncogenic transcription factor RUNX2 is widely upregulated in the head and neck squamous cell carcinoma (HNSCC) with lymph node metastasis, where it also predicts poor prognosis in patients with HNSCC. Enforced expression of ectopic RUNX2 promoted the metastatic capabilities of HNSCC, whereas RUNX2 silencing inhibited these features. Mechanistic investigations showed that manipulating levels of activin A (INHBA) could rescue or compromise the RUNX2-mediated metastatic capabilities of HNSCC cells. Furthermore, we found that miR-376c-3p encoded within the 3′-untranslated region of RUNX2 played a pivotal role in regulating RUNX2 expression in highly metastatic HNSCC cells, where it was downregulated commonly. Restoring miR-376c expression in this setting suppressed expression of RUNX2/INHBA axis along with metastatic capability. Clinically, we observed an inverse relationship between miR-376c-3p expression and the RUNX2/INHBA axis in HNSCC specimens. In summary, our results defined a novel pathway in which dysregulation of the RUNX2/INHBA axis due to miR-376c downregulation fosters lymph node metastasis in HNSCC.
原文英語
頁(從 - 到)7140-7150
頁數11
期刊Cancer Research
76
發行號24
DOIs
出版狀態已發佈 - 十二月 15 2016

    指紋

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此

Chang, W. M., Lin, Y. F., Su, C. Y., Peng, H. Y., Chang, Y. C., Lai, T. C., Wu, G. H., Hsu, Y. M., Chi, L. H., Hsiao, J. R., Chen, C. L., Chang, J. Y., Shieh, Y. S., Hsiao, M., & Shiah, S. G. (2016). Dysregulation of RUNX2/activin-A axis upon miR-376c downregulation promotes lymph node metastasis in head and neck squamous cell carcinoma. Cancer Research, 76(24), 7140-7150. https://doi.org/10.1158/0008-5472.CAN-16-1188