Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.
Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.
复制标题
DOI：
10.12659/msm.895788
复制
发表时间：
2016-04-11
期刊：
影响因子：
--
通讯作者：
Qu J
中科院分区：
文献类型：
--
作者：
Sun D;Han S;Liu C;Zhou R;Sun W;Zhang Z;Qu J
本研究旨在探讨miR-199 a-5 p在甲状腺癌发生发展中的作用，包括其抗增殖作用和下游信号通路。我们采用qRT-PCR方法检测了42例甲状腺滤泡癌患者和42例正常人中几种microRNA的表达。我们确定CTGF为miR-491的靶点，并在用CTGF siRNA、miR-199 a模拟物或抑制剂转染的FTC-133细胞中测定活力和细胞周期状态。我们发现与对照组相比，甲状腺滤泡癌组织样本中miR-199 a-5 p表达不足。通过信息学分析和荧光素酶报告基因分析，证实CTGF是miR-199 a-5 p作用于甲状腺细胞的靶点。此外，我们发现CTGF的mRNA和蛋白表达水平在恶性组织中均明显高于良性组织。miR-199 a-5 p模拟物和CTGF siRNA同样下调CTGF的表达，并通过将细胞周期阻滞在G 0期来降低FTC-133细胞的活力。转染miR-199 a-5 p抑制剂可增加CTGF的表达，并通过增加G2/M期和S期细胞比例来促进细胞活力。我们的研究证明CTGF基因是miR-199 a-5 p的靶基因，证明CTGF和miR-199 a之间存在负相关关系。提示miR-199 a-5 p可能成为甲状腺滤泡癌治疗的新靶点。
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. 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. 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. 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.