miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

被引：72

作者：

Boufraqech, Myriem ^{[1
]}

Nilubol, Naris ^{[1
]}

Zhang, Lisa ^{[1
]}

Gara, Sudheer Kumar ^{[1
]}

Sadowski, Samira M. ^{[1
]}

Mehta, Amit ^{[1
,2
]}

He, Mei ^{[1
]}

Davis, Sean ^{[3
]}

Dreiling, Jennifer ^{[4
]}

Copland, John A. ^{[5
]}

Smallridge, Robert C. ^{[5
,6
]}

Quezado, Martha M. ^{[4
]}

Kebebew, Electron ^{[1
]}

机构：

[1] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] Geisel Sch Med Dartmouth, Hanover, NH USA

[3] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[4] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[5] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA

[6] Mayo Clin, Div Endocrinol, Dept Internal Med, Jacksonville, FL 32224 USA

来源：

CANCER RESEARCH | 2015年 / 75卷 / 02期

关键词：

LYSYL OXIDASE; DOWN-REGULATION; BETA-AMINOPROPIONITRILE; MESENCHYMAL TRANSITION; MICRORNAS; CARCINOMA; CELLS; METASTASIS; DIFFERENTIATION; MALIGNANCY;

D O I：

10.1158/0008-5472.CAN-14-2304

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：367 / 377

页数：11

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