Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.

Abstract

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.

• Authors: Dawei Sun, Shen Han, Chao Liu, Rui Zhou, Weihai Sun, Zhijun Zhang, Jianjun Qu
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 22 Pg. 1210-7 (Apr 11 2016) ISSN: 1643-3750 [Electronic] United States
• PMID: 27062921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCN2 protein, human
• MicroRNAs
• mirn199 microRNA, human
• Connective Tissue Growth Factor

Topics

• Adenocarcinoma, Follicular (genetics, metabolism, pathology)
• Case-Control Studies
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Connective Tissue Growth Factor (antagonists & inhibitors, genetics, metabolism)
• Down-Regulation
• Female
• Gene Expression
• Genes, Tumor Suppressor
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Real-Time Polymerase Chain Reaction
• Signal Transduction
• Thyroid Neoplasms (genetics, metabolism, pathology)
• Transfection