1. miRNA-106a directly targeting RARB associates with the expression of Na+/I− symporter in thyroid cancer by regulating MAPK signaling pathway
- Author
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Zhong-Ling Qiu, Chen-Tian Shen, Weijun Wei, Hong-Jun Song, and Quan-Yong Luo
- Subjects
0301 basic medicine ,Sodium-iodide symporter ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Cell Survival ,MAP Kinase Signaling System ,Receptors, Retinoic Acid ,Retinoic acid receptor beta ,Biology ,Thyroid cancer ,Thyroid carcinoma ,RARB ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,MTT assay ,Viability assay ,Thyroid Neoplasms ,3' Untranslated Regions ,Cell Proliferation ,Symporters ,Research ,Receptors, Thyrotropin ,Middle Aged ,medicine.disease ,Carcinoma, Papillary ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Oncology ,miR-106a ,Thyroid Cancer, Papillary ,030220 oncology & carcinogenesis ,Symporter ,Cancer research ,MAPK signaling pathway ,Female ,Iodine - Abstract
Background 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. Methods Expression 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. Results Compared 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. Conclusions miRNA-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.
- Published
- 2016