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

• Main Authors: Xiaoli Liu, Yantao Fu, Guang Zhang, Daqi Zhang, Nan Liang, Fang Li, Changlin Li, Chengqiu Sui, Jinxi Jiang, Hongzhi Lu, Zihan Zhao, Gianlorenzo Dionigi, Hui Sun
• Format: Article
• Language: English
• Published: Elsevier 2019-12-01
• Series: Molecular Therapy: Oncolytics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770519300981

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. Keywords: miR-424-5p, anoikis resistance, lung metastasis, Hippo signaling and thyroid cancer