title: 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.affiliation: Thyroid Department of Affiliated Hospital of Qingdao University, Qingdao Key Laboratory of Thyroid Diseases, Qingdao, Shandong, China (mainland).
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.affiliation: , Guizhou Tongren Vocational and Technical College of Pharmaceutical Sciences, Guizhou, China (mainland).
authors.forename: Shen
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of General Surgery, People's Hospital of Zhangqiu City, Jinan, Shandong, China (mainland).
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: , Teaching and Research Section of Medicine and Health Management of Medical College of Qingdao University, Qingdao, Shandong, China (mainland).
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Thyroid Department of Affiliated Hospital of Qingdao University, Qingdao Key Laboratory of Thyroid Diseases, Qingdao, Shandong, China (mainland).
authors.forename: Weihai
authors.initials: W
authors.lastname: Sun
authors.affiliation: , Linzi District of Zibo City People's Hospital of Hepatobiliary Surgery, Zibo, Shangdong, China (mainland).
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Weifang People's Hospital, Weifang, Shandong, China (mainland).
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qu
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: C526317:CCN2 protein, human; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D055513:Connective Tissue Growth Factor