miR30a inhibits LOX expression and anaplastic thyroid cancer progression

Myriem Boufraqech, Naris Nilubol, Lisa Zhang, Sudheer Kumar Gara, Samira M. Sadowski, Amit Mehta, Mei He, Sean Davis, Jennifer Dreiling, John A III Copland, Robert Christian Smallridge, Martha M. Quezado, Electron Kebebew

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36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalCancer Research
Volume75
Issue number2
DOIs
StatePublished - Aug 8 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Boufraqech, M., Nilubol, N., Zhang, L., Gara, S. K., Sadowski, S. M., Mehta, A., He, M., Davis, S., Dreiling, J., Copland, J. A. III., Smallridge, R. C., Quezado, M. M., & Kebebew, E. (2015). miR30a inhibits LOX expression and anaplastic thyroid cancer progression. Cancer Research, 75(2), 367-377. https://doi.org/10.1158/0008-5472.CAN-14-2304