miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2

被引:53
作者
Gao, Peng [1 ]
Wang, Huan [1 ]
Yu, Jiarui [1 ]
Zhang, Jie [2 ]
Yang, Zhao [1 ]
Liu, Meiyue [1 ]
Niu, Yi [1 ]
Wei, Xiaomei [1 ]
Wang, Wei [1 ]
Li, Hongmin [2 ]
Wang, Yadi [3 ]
Sun, Guogui [1 ]
机构
[1] North China Univ Sci & Technol, Affiliated Peoples Hosp, Dept Radiat Oncol, Tangshan, Peoples R China
[2] North China Univ Sci & Technol, Affiliated Peoples Hosp, Dept Pathol, Tangshan, Peoples R China
[3] PLA Army Gen Hosp, Dept Radiat Oncol, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
CIRCULATING MICRORNAS; BREAST-CANCER; TUMOR-GROWTH; BETA; METASTASIS; PROLIFERATION; INHIBITION; BIOMARKERS; APOPTOSIS; SURVIVAL;
D O I
10.1371/journal.pgen.1007790
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.
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页数:22
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