miR-296 inhibits the metastasis and epithelial-mesenchymal transition of colorectal cancer by targeting S100A4

被引:66
作者
He, Zheng [1 ]
Yu, Lianhua [2 ]
Luo, Shiyi [3 ,4 ]
Li, Mingzhen [5 ]
Li, Junbo [5 ]
Li, Qi [6 ]
Sun, Yi [1 ]
Wang, Chengbin [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Clin Lab, 28 Fuxing Rd, Beijing 100853, Peoples R China
[2] Taizhou Municipal Hosp, Dept Lab Med, Taizhou 318000, Peoples R China
[3] Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China
[4] Xiamen Univ, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China
[5] Beijing Ctr Phys & Chem Anal, Beijing 100094, Peoples R China
[6] China Acad Chinese Med Sci, Xiyuan Hosp, Dept Clin Lab, Beijing 100091, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-296; Colorectal cancer; Metastasis; Epithelial-mesenchymal transition; S100A4; MICRORNAS; BIOMARKERS; EMT;
D O I
10.1186/s12885-017-3121-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers. However, the status of miR-296 and its function in CRC remain unknown. Methods: The expression of miR-296 was confirmed by qRT-PCR in CRC tissues and cells, and its level was altered by corresponding miRNA vectors. Wound healing and Transwall assays were performed to detect the migration and invasion of CRC cells. The levels of proteins were measured using immunoblotting, immunohistochemistry and immunofluorescence. Results: Underexpression of miR-296 was disclosed in CRC tissues and cells. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of CRC patients. In vitro experiments indicated that miR-296 inhibited CRC cell migration and invasion. Mechanically, miR-296 inhibited the epithelial-mesenchymal transition (EMT) of CRC cells. A negative correlation between miR-296 and S100A4 expression was observed in CRC tissues. Luciferase reporter assays indicated that miR-296 inversely regulated the luciferase activity of 3'-UTR of S100A4. Herein, S100A4 was found to be a downstream molecule of miR-296 in CRC. Furthermore, S100A4 mediated the anti-metastatic effects of miR-296 on EMT, migration and invasion of CRC cells. Conclusions: miR-296 functions as an anti-metastatic factor mainly by suppressing S100A4 in CRC. It potentially acts as a prognostic predictor and a drug-target for CRC patients.
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页数:10
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