miR30a inhibits LOX expression and anaplastic thyroid cancer progression

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downr...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2015-01, Vol.75 (2), p.367-377
Main Authors: Boufraqech, Myriem, Nilubol, Naris, Zhang, Lisa, Gara, Sudheer Kumar, Sadowski, Samira M, Mehta, Amit, He, Mei, Davis, Sean, Dreiling, Jennifer, Copland, John A, Smallridge, Robert C, Quezado, Martha M, Kebebew, Electron
Format: Article
Language:English
Subjects:
Animals
Cell Movement - genetics
Disease Progression
Down-Regulation
Female
Gene Knockdown Techniques
Heterografts
Humans
Mice
Mice, Nude
MicroRNAs - biosynthesis
MicroRNAs - genetics
Neoplasm Invasiveness
Protein-Lysine 6-Oxidase - antagonists & inhibitors
Protein-Lysine 6-Oxidase - biosynthesis
Protein-Lysine 6-Oxidase - genetics
Thyroid Carcinoma, Anaplastic - enzymology
Thyroid Carcinoma, Anaplastic - genetics
Thyroid Carcinoma, Anaplastic - pathology
Thyroid Neoplasms - enzymology
Thyroid Neoplasms - genetics
Thyroid Neoplasms - pathology
Transfection
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Summary:Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelial-mesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-14-2304