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 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 eluc...

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Bibliographic Details
Published in:Molecular therapy. Oncolytics 2019-12, Vol.15, p.248-260
Main Authors: Liu, Xiaoli, Fu, Yantao, Zhang, Guang, Zhang, Daqi, Liang, Nan, Li, Fang, Li, Changlin, Sui, Chengqiu, Jiang, Jinxi, Lu, Hongzhi, Zhao, Zihan, Dionigi, Gianlorenzo, Sun, Hui
Format: Article
Language:English
Subjects:
Anoikis
anoikis resistance
Apoptosis
Bioinformatics
Cell growth
Colonization
Gene expression
Genomes
Hippo signaling and thyroid cancer
Immunofluorescence
Kinases
Lung cancer
lung metastasis
Medical prognosis
Metastases
Metastasis
MicroRNAs
miR-424-5p
Proteins
Therapeutic applications
Thyroid cancer
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Summary: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.
ISSN:2372-7705
2372-7705
DOI:10.1016/j.omto.2019.10.008