miR-424-5p has been widely identified to function as an oncomiR 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 metastasis colonization models in vivo and functional assays in vitro were used to determine the role of miR-424-5p in thyroid cancer. 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 significantly 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 metastasis by inactivating Hippo signaling via simultaneously targeting 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.

miR-424-5p已被广泛鉴定为在多种人类癌症类型中的癌基因功能。但是，miR-424-5p在甲状腺癌远处转移中的生物学功能及其潜在机制尚不清楚。在当前的研究中，从癌症基因组图谱（TCGA）中阐明了10个配对的新鲜甲状腺癌组织和甲状腺癌数据集中的miR-424-5p表达。体内肺转移定植模型和体外功能测定用于确定miR-424-5p在甲状腺癌中的作用。应用生物信息学分析，蛋白质印迹，荧光素酶报告基因和免疫荧光分析法，以确定与miR-424-5p在甲状腺癌肺癌转移中的功能有关的潜在靶标和潜在机制。在这里，我们报道了甲状腺癌中miR-424-5p的表达上调，而miR-424-5p的过表达与甲状腺癌的远处转移密切相关。促进miR-424-5p的上调，而沉默miR-424-5p的则抑制了体外的无神经耐药性和体内的肺转移。机理研究进一步揭示，miR-424-5p通过同时靶向WWC1，SAV1和LAST2来灭活Hippo信号传导，从而促进了厌食症的抵抗和肺转移。因此，我们的结果支持了miR-424-5p可以作为甲状腺癌肺转移中潜在的治疗靶点的想法。