miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway

  • Authors:
    • Zongyu Li
    • Xin Huang
    • Jinkai Xu
    • Qinghua Su
    • Jun Zhao
    • Jiancang Ma
  • View Affiliations

  • Published online on: August 18, 2016     https://doi.org/10.3892/ijo.2016.3659
  • Pages: 1629-1637
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and represent approximately 80% of all thyroid cancers. The present study is aimed to investigate the role of microRNA (miR)-449 in the progression of PTC. Our results revealed that miR-449 was underexpressed in the collected PTC specimens compared with non-cancerous PTC tissues. Overexpression of miR-449 induced a cell cycle arrest at G0/G1 phase and inhibited PTC cell growth in vitro. Further studies revealed that RET proto-oncogene (RET) is a novel miR-449 target, due to miR-449 bound directly to its 3'-untranslated region and miR-449 mimic reduced the protein expression of RET. Similar to the effects of miR-449 overexpression, RET downregulation inhibited cell growth, whereas RET overexpression reversed the inhibitive effect of miR-449 mimic. Furthermore, miR-449 overexpression inhibited the nuclear translocation of β-catenin and reduced the expression of several downstream genes, including c-Myc, cyclin D1, T cell-specific transcription factor (TCF) and lymphoid enhancer-binding factor 1 (LEF-1), and inactivated the β-catenin pathway in TPC-1 cells. Moreover, overexpression of β-catenin prevented miR-449-reduced cell cycle arrest and cell viability. In xenograft animal experiments, miR-449 overexpression effectively suppressed the tumor growth of PTC. Taken together, our research indicated that miR-449 functions as an anti-oncogene by targeting RET, and that miR-449 overexpression inhibited the growth of PTC by inactivating the β-catenin pathway. Thus, miR-449 may serve as a potential therapeutic strategy for the treatment of PTC.
View Figures
View References

Related Articles

Journal Cover

October-2016
Volume 49 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Huang X, Xu J, Su Q, Zhao J and Ma J: miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway. Int J Oncol 49: 1629-1637, 2016
APA
Li, Z., Huang, X., Xu, J., Su, Q., Zhao, J., & Ma, J. (2016). miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway. International Journal of Oncology, 49, 1629-1637. https://doi.org/10.3892/ijo.2016.3659
MLA
Li, Z., Huang, X., Xu, J., Su, Q., Zhao, J., Ma, J."miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway". International Journal of Oncology 49.4 (2016): 1629-1637.
Chicago
Li, Z., Huang, X., Xu, J., Su, Q., Zhao, J., Ma, J."miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway". International Journal of Oncology 49, no. 4 (2016): 1629-1637. https://doi.org/10.3892/ijo.2016.3659