miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/[beta]-Catenin Pathway in Tongue Squamous Cell Carcinoma

• Published in: BioMed research international 2017-01, Vol.2017
• Main Authors: Weng, Junquan, Zhang, Hui, Wang, Cheng, Liang, Jianfeng, Chen, Guanhui, Li, Wenqing, Tang, Haikuo, Hou, Jinsong
• Format: Article
• Language: English
• Subjects: Biomedical research; Cancer; Epithelial cells; Gene expression; Genetic aspects; Kinases; Medical prognosis; Metastasis; Mutation; Squamous cell carcinoma; Studies
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2017/6010926

MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.