MicroRNA-485-5p suppresses growth and metastasis in non-small cell lung cancer cells by targeting IGF2BP2

被引:60
|
作者
Huang, Ri-sheng [1 ,2 ]
Zheng, Yuan-liang [1 ]
Li, Chang [2 ]
Ding, Cheng [2 ]
Xu, Chun [2 ]
Zhao, Jun [2 ]
机构
[1] Wenzhou Cent Hosp, Dept Thorac Surg, Wenzhou, Peoples R China
[2] Soochow Univ, Affiliated Hosp 1, Dept Thorac Surg, 899 Pinghai Rd, Suzhou 215000, Peoples R China
关键词
IGF2BP2; Metastasis; miR-485-5p; Non-small cell lung cancer; Tumor survival; EPITHELIAL-MESENCHYMAL TRANSITION; GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA; PROLIFERATION; PROGRESSION; MIR-485-5P; INVASION;
D O I
10.1016/j.lfs.2018.03.005
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
miR-485-5p serves as a tumor suppressor in several types of cancers. However, its prognostic and biological significance in non-small cell lung cancer (NSCLC) have not been determined yet. In the present study, we checked the expression of miR-485-5p in 87 pairs of paraffin-embedded lung cancer and matched non-cancerous specimens. The associations of miR-485-5p expression with aggressive parameters and survival in NSCLC were investigated. In addition, the function of miR-485-5p in controlling tumor growth and metastasis was clarified. We found that miR-485-5p was significantly downregulated in NSCLC, relative to adjacent non-cancerous lung tissues. Low miR-485-5p expression was significantly associated with advanced TNM stage, lymph node metastasis, and reduced patient survival. Overexpression of miR-485-5p significantly suppressed the growth and invasion, while knockdown of miR-485-5p had an opposite effect. Moreover, miR-485-5p overexpression caused a G0/G1 cell-cycle arrest and impaired TGF-beta-induced epithelial-mesenchymal transition. Mechanistically, IGF2BP2 was identified as a novel direct target of miR-485-5p. Depletion of IGF2BP2 significantly inhibited NSCLC cell proliferation and invasion. Enforced expression of IGF2BP2 reversed the tumor suppressive activity of miR-485-5p. In vivo studies further demonstrated that overexpression of miR-485-5p interfered with the growth and metastasis of A549 cells in mice and reduced the expression of IGF2BP2. In conclusion, low miR-485-5p expression predicts poor prognosis in NSCLC patients. The miR-485-5p/IGF2BP2 axis orchestrates the growth and metastasis of NSCLC and represents a potential therapeutic target for this disease.
引用
收藏
页码:104 / 111
页数:8
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