The Tumor Suppressive Role of MiRNA-509-5p by Targeting FOXM1 in Non-Small Cell Lung Cancer

被引:42
作者
Ma, Ning [1 ]
Zhana, Weihua [1 ]
Qiao, Chenhui [1 ]
Luo, Hong [1 ]
Zhang, Xin [1 ]
Liu, Donghai [1 ]
Zang, Suhua [1 ]
Zhang, Liang [1 ]
Bai, Jingyun [2 ]
机构
[1] Zhengzhou Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Dept Nephrol, Affiliated Hosp 1, 1 East Jianshe Rd, Zhengzhou 450052, Peoples R China
关键词
MiRNA-509-5p; FOXM1; Non-small cell lung cancer; Apoptosis; Migration; Invasion; TRANSCRIPTION FACTOR; METASTASIS; MICRORNAS; MIGRATION;
D O I
10.1159/000443086
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Deregulation of microRNAs (miRNAs) expression is a frequent event in cancer development and progression. Recent studies have implied that abnormal expression of miRNAs is frequently observed in non-small cell lung cancer (NSCLC). Here, we examined the levels and biological functions of miR-509-5p in NSCLC. Methods: The levels of miR-509-5p were measured by real-time quantitative PCR (RT-PCR) in NSCLC cell lines and NSCLC tissues along with adjacent normal tissues. Cell viability was analyzed by MTT and colony formation assay. Cell migration and invasion were evaluated by transwell and wound healing assay. In addition, we predicted the putative targets of miR-509-5p by bioinformatics analyses. Moreover, by luciferase-reporter assay, we analyzed the relationship between miR-509-5p and the target in NSCLC cells. Results: miR-509-5p expression was significantly reduced in NSCLC tissues compared with adjacent normal tissues. In addition, miR-509-5p decreased cell proliferation, migration and invasive capability of NSCLC cells. Moreover, we found that FOXM1 was a putative target of miR-509-5p. Enforced miR-509-5p expression in NSCLC cells reduced both mRNA and protein levels of FOXM1. Furthermore, dual-luciferase reporter assay showed miR-509-5p could bind to the 3' untranslational regions of FOXM1 mRNA. Furthermore, overexpression of FOXM1 reversed cell viability, migration, invasion and vimentin levels suppressed by miR-509-5p mimics in H1299 cells. Conclusions: miR-509-5p exerts tumor-suppressive effects by attenuating FOXM1 in NSCLC. Collectively, these findings provide further evidence that miR-509-5p may be considered as a novel and potential target for the diagnosis, prognosis and treatment of NSCLC. (C) 2016 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:1435 / 1446
页数:12
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