MiR-646 suppresses proliferation and metastasis of non-small cell lung cancer by repressing FGF2 and CCND2

被引:30
作者
Wang, Jing [1 ]
Shu, Huizhen [2 ]
Guo, Shuigen [3 ]
机构
[1] Fudan Univ, Dept Resp Dis, Jinshan Hosp, Shanghai, Peoples R China
[2] Xuanqiao Community Hlth Serv Ctr, Shanghai, Peoples R China
[3] Fudan Univ, Shanghai Pudong Hosp, Dept Resp Dis, Pudong Med Ctr, Shanghai 201399, Peoples R China
来源
CANCER MEDICINE | 2020年 / 9卷 / 12期
关键词
CCND2; FGF2; miR-646; non-small cell lung cancer; GROWTH; PROGRESSION;
D O I
10.1002/cam4.3062
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNA-646 (miR-646) has been implicated in several other cancers; however, its functional mechanism in non-small cell lung cancer (NSCLC) remains unclear. In this study, we observed the downregulation of miR-646 expression in NSCLC tissues and cell lines. Low-level expression of miR-646 was associated with metastasis and stage of NSCLCs. Functional assays showed that overexpression of miR-646 could suppress NSCLC cell proliferation, clonogenicity, invasion, and inhibit epithelial-mesenchymal transition (EMT), whereas decreased miR-646 expression showed the opposite effects. Importantly, miR-646 overexpression attenuated in vivo tumor growth and metastasis in nude mice models. Mechanically, miR-646 directly targeted and suppressed fibroblast growth factor 2 (FGF2) and cyclin D2 (CCND2) expression. Reintroduction of FGF2 and CCND2 attenuated miR-646-mediated suppression of proliferation and invasion in NSCLC. Collectively, these results demonstrate that miR-646 acts as a tumor suppressor in NSCLC by targeting FGF2 and CCND2, and may serve as a therapeutic target for patients with NSCLC.
引用
收藏
页码:4360 / 4370
页数:11
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