miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

被引：123

作者：

Boufraqech, Myriem ^{[1
]}

Zhang, Lisa ^{[1
]}

Jain, Meenu ^{[1
]}

Patel, Dhaval ^{[1
]}

Ellis, Ryan ^{[1
]}

Xiong, Yin ^{[1
]}

He, Mei ^{[1
]}

Nilubol, Naris ^{[1
]}

Merino, Maria J. ^{[2
]}

Kebebew, Electron ^{[1
]}

机构：

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

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

来源：

基金：

美国国家卫生研究院;

关键词：

miR-145; thyroid cancer; AKT3; metastasis; biomarker; EPITHELIAL-MESENCHYMAL TRANSITION; C-MYC; MICRORNAS; EXPRESSION; SURVIVAL; PATHWAY; CELLS; MECHANISM; PAPILLARY; EXCHANGE;

D O I：

10.1530/ERC-14-0077

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

引用

页码：517 / 531

页数：15

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