MicroRNA-126 suppresses proliferation of undifferentiated (BRAF{sup V600E} and BRAF{sup WT}) thyroid carcinoma through targeting PIK3R2 gene and repressing PI3K-AKT proliferation-survival signalling pathway
- Cancer Molecular Pathology, School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland (Australia)
Background: The objectives of this study are to investigate the expression of miR-126 and evaluate its effect on proliferation in undifferentiated thyroid carcinoma. Methods: miR-126 expression of undifferentiated thyroid carcinoma cell lines 8505C (BRAF{sup V600E/V600E}), BHT-101 (BRAF{sup V600E/WT}) and MB-1 (BRAF{sup WT/WT}) were quantified with q-PCR. These cell lines were transiently transfected with exogenous miR-126 (mimic). Following transfection, proliferation effects were observed through MTS proliferation assay and colony formation abilities. Immunofluorescence imaging and Western blot assay were also done to check target proteins expression. Results: Under-expression (p<0.05) of miR-126 was noted in BRAF{sup V600E} mutated undifferentiated thyroid carcinoma cells (8505C and BHT-101), but no change in expression was noted in non BRAF{sup V600E} mutated undifferentiated thyroid carcinoma cells (MB-1). In addition, a 30–50% drop in proliferation ability and a 35–45% reduction in colony formation capability were noticed in miR-126 mimic transfected group when compared to control group. Furthermore, immunofluorescence images showed reduced expression of p85β and p-AKT protein in miR-126 mimic transfected cells when compared to un-transfected cells. Also, Western blot analysis revealed a 34–40% suppression of p85β protein and a 21–53% drop in active AKT kinase (p-AKT) protein in miR-126 mimic transfected group when compared to control group. Conclusions: Expression of miR-126 was down-regulated in BRAF{sup V600E} mutated undifferentiated thyroid carcinoma. In addition, miR-126 was found to act as proliferation suppressor targeting PIK3R2 gene and reducing p85β (a regulatory subunit of PI3K kinase) protein translation and lower AKT kinase activity. Therefore, miR-126 could be a potential therapeutic tool in the treatment of undifferentiated thyroid carcinoma. - Highlights: • miR-126 expression was low in BRAF mutated undifferentiated thyroid carcinoma. • miR-126 suppresses p85β expression in undifferentiated thyroid carcinoma. • miR-126 suppresses AKT kinase activity in undifferentiated thyroid carcinoma. • miR-126 suppresses proliferation of undifferentiated thyroid carcinoma.
- OSTI ID:
- 22746388
- Journal Information:
- Experimental Cell Research, Vol. 339, Issue 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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