11 April 2016 : Laboratory Research
Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid CarcinomaDawei SunABC, Shen HanABCDE, Chao LiuBC, Rui ZhouDE, Weihai SunCDE, Zhijun ZhangABCDEFG, Jianjun QuBCDF
Med Sci Monit 2016; 22:1210-2117
BACKGROUND: The objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway.
MATERIAL AND METHODS: We conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors.
RESULTS: We identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases.
CONCLUSIONS: Our study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.
Keywords: Adenocarcinoma, Follicular - pathology, Case-Control Studies, Connective Tissue Growth Factor - metabolism, Gene Expression, Real-Time Polymerase Chain Reaction, Signal Transduction, Thyroid Neoplasms - pathology
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