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

Li,Zongyu; Huang,Xin; Xu,Jinkai; Su,Qinghua; Zhao,Jun; Ma,Jiancang

doi:10.3892/ijo.2016.3659

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
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Affiliations: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of General Surgery, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: August 18, 2016 https://doi.org/10.3892/ijo.2016.3659
Pages: 1629-1637

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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.

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