MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer

被引：89

作者：

Zhang, P. ^{[1
]}

Tang, W. M. ^{[1
]}

Zhang, H. ^{[1
,2
]}

Li, Y. Q. ^{[1
]}

Peng, Y. ^{[1
]}

Wang, J. ^{[1
]}

Liu, G. N. ^{[1
]}

Huang, X. T. ^{[1
]}

Zhao, J. J. ^{[3
]}

Li, G. ^{[4
]}

Li, A. M. ^{[1
]}

Bai, Y. ^{[1
]}

Chen, Y. ^{[1
]}

Ren, Y. X. ^{[1
]}

Li, G. X. ^{[5
]}

Wang, Y. D. ^{[1
]}

Liu, S. D. ^{[1
]}

Wang, J. D. ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China

[2] Southern Med Univ, Hexian Mem Affiliated Hosp, Dept Gastroenterol, Guangzhou 511400, Guangdong, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Rheumatism, Guangzhou 510515, Guangdong, Peoples R China

[4] Southern Med Univ, Nanfang Hosp, Dept Otolaryngol Head & Neck Surg, Guangzhou 510515, Guangdong, Peoples R China

[5] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China

来源：

BRITISH JOURNAL OF CANCER | 2017年 / 117卷 / 04期

关键词：

MiR-646; FOXK1; gastric cancer; metastasis; epithelial-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITION; MICRORNA EXPRESSION; COLORECTAL-CANCER; OVARIAN-CANCER; CARCINOMA; INVASION; DEREGULATION; HIF-1-ALPHA; PATHWAY; GROWTH;

D O I：

10.1038/bjc.2017.181

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. Methods: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice. Results: MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial-mesenchymal transition (EMT)-associated proteins. TGF-beta 1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-beta 1- induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1. Conclusions: miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.

引用

页码：525 / 534

页数：10

共 38 条

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