Abstract
BackgroundSerum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed. These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated.MethodsExpression levels of six identified miRNAs were assessed via quantitative real-time PCR (qRT-PCR) in the serum of eligible patients. Dual-luciferase reporter assay was used to determine the potential target of miR-106a. Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The change of gene expression was detected by qRT-PCR and western blotting analysis. In vitro iodine uptake assay was conducted by a γ-counter.ResultsCompared to PTC patients with 131I-avid lung metastases, miR-106a was up-regulated in the serum of patients with non-131I-avid lung metastases. The results of dual-luciferase reporter assay demonstrated that miR-106a directly targeted retinoic acid receptor beta (RARB) 3′-UTR. miR-106a-RARB promoted viability of thyroid cancer cells by regulating MEKK2-ERK1/2 and MEKK2-ERK5 pathway. miR-106a-RARB inhibited apoptosis of thyroid cancer cells by regulating ASK1-p38 pathway. Moreover, miR-106a-RARB could regulate the expression of sodium iodide symporter, TSH receptor and alter the iodine uptake function of thyroid cancer cells.ConclusionsmiRNA-106a, directly targeting RARB, associates with the viability, apoptosis, differentiation and the iodine uptake function of thyroid cancer cell lines by regulating MAPK signaling pathway in vitro. These findings in the present study may provide new strategies for the diagnosis and treatment in radioiodine-refractory differentiated thyroid carcinoma.
Highlights
Serum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed
It is well accepted that constitutive activation of mitogenactivated protein kinase (MAPK) signaling pathway plays a significant role in the tumorigenesis of thyroid carcinoma and it could promote the dedifferentiation of thyroid-cancer cells
MiR-106a is differently expressed in different thyroid cancer cell lines and altered after transfection Expression levels of miR-106a were detected in CGTHW3 and 8505C cells by quantitative real-time PCR (qRT-PCR)
Summary
Serum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated. It is well accepted that constitutive activation of mitogenactivated protein kinase (MAPK) signaling pathway plays a significant role in the tumorigenesis of thyroid carcinoma and it could promote the dedifferentiation of thyroid-cancer cells. Regarding to this fact, diseasespecific molecular targets of therapy is studied much popularly [6]. Lakshmanan et al found that miR-339-5p directly bound to hNIS-3′UTR and miR-339-5p overexpression decreased NIS-mediated radioiodine uptake in HEK293 cells expressing exogenous hNIS [16]
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