title: miR30a inhibits LOX expression and anaplastic thyroid cancer progression.
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.
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Myriem
authors.initials: M
authors.lastname: Boufraqech
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Sudheer Kumar
authors.initials: SK
authors.lastname: Gara
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Sadowski
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Amit
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Mei
authors.initials: M
authors.lastname: He
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Sean
authors.initials: S
authors.lastname: Davis
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dreiling
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida.
authors.forename: John A
authors.initials: JA
authors.lastname: Copland
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida. Endocrinology Division, Internal Medicine Department, Mayo Clinic, Jacksonville, Florida.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smallridge
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Quezado
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. kebebewe@mail.nih.gov.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D065646:Thyroid Carcinoma, Anaplastic / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D014162:Transfection
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D008249:Protein-Lysine 6-Oxidase