Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 49, Issue 4, Pages 1629-1637Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3659
Keywords
papillary thyroid carcinoma; microRNA-449; RET proto-oncogene; beta-catenin
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Funding
- Science and Technology Plan Project of Social Development Plans for Public Relations of Shaanxi Province, China [2012SF2-13, 2015SF068]
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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 GO/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 beta-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 beta-catenin pathway in TPC-1 cells. Moreover, overexpression of beta-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 beta-catenin pathway. Thus, miR-449 may serve as a potential therapeutic strategy for the treatment of PTC.
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