miR-424-5p Promotes Anoikis Resistance and Lung Metastasis by Inactivating Hippo Signaling in Thyroid Cancer

miR-424-5p has been widely identified to function as an onco- miR in multiple human cancer types. However, the biological function of miR-424-5p in distant metastasis of thyroid cancer, as well as the underlying mechanism, remains not clarified yet. In the current study, miR-424-5p expression was elucidated in 10 paired fresh thyroid cancer tissues and the thyroid cancer dataset from The Cancer Genome Atlas (TCGA). Lung metas- tasis colonization models in vivo and functional assays in vitro were used to determine the role of miR-424-5p in thyroid can- cer. Bioinformatics analysis, western blot, luciferase reporter, and immunofluorescence assays were applied to identify the potential targets and underlying mechanism involved in the functional role of miR-424-5p in lung metastasis of thyroid cancer. Here, we reported that miR-424-5p was upregulated in thyroid cancer, and overexpression of miR-424-5p signifi- cantly correlated with distant metastasis of thyroid cancer. Upregulating miR-424-5p promoted, whereas silencing miR-424-5p inhibited, anoikis resistance in vitro and lung metastasis in vivo. Mechanistic investigation further revealed that miR-424-5p promoted anoikis resistance and lung metas- tasis by inactivating Hippo signaling via simultaneously target- ing WWC1, SAV1, and LAST2. Therefore, our results support the idea that miR-424-5p may serve as a potential therapeutic target in lung metastasis of thyroid cancer.