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

© 2014 Society for Endocrinology..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

Endocrine-related cancer - 21(2014), 4 vom: 30. Aug., Seite 517-31

Sprache:

Englisch

Beteiligte Personen:

Boufraqech, Myriem [VerfasserIn]
Zhang, Lisa [VerfasserIn]
Jain, Meenu [VerfasserIn]
Patel, Dhaval [VerfasserIn]
Ellis, Ryan [VerfasserIn]
Xiong, Yin [VerfasserIn]
He, Mei [VerfasserIn]
Nilubol, Naris [VerfasserIn]
Merino, Maria J [VerfasserIn]
Kebebew, Electron [VerfasserIn]

Links:

Volltext

Themen:

AKT3
AKT3 protein, human
Biomarker
EC 2.7.1.-
EC 2.7.11.1
Journal Article
MIRN145 microRNA, human
Metastasis
MiR-145
MicroRNAs
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Thyroid cancer
Vascular Endothelial Growth Factor A
Vascular endothelial growth factor A, mouse

Anmerkungen:

Date Completed 09.02.2015

Date Revised 21.03.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1530/ERC-14-0077

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM237814285