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MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4

Authors :
Hui Li
Ruoyun Ouyang
Zi Wang
Weihua Zhou
Huiyong Chen
Yawen Jiang
Yibin Zhang
Mengting Liao
Weiwei Wang
Mao Ye
Zhigang Ding
Xueping Feng
Jing Liu
Bin Zhang
Source :
Scientific Reports
Publication Year :
2016
Publisher :
Nature Publishing Group, 2016.

Abstract

Previous studies have shown that dysregulation of microRNA-150 (miR-150) is associated with aberrant proliferation of human non-small cell lung cancer (NSCLC) cells. However, whether miR-150 has a critical role in NSCLC cell metastasis is unknown. Here, we reveal that the critical pro-metastatic role of miR-150 in the regulation of epithelial-mesenchymal-transition (EMT) through down-regulation of FOXO4 in NSCLC. In vitro, miR-150 targets 3′UTR region of FOXO4 mRNA, thereby negatively regulating its expression. Clinically, the expression of miR-150 was frequently up-regulated in metastatic NSCLC cell lines and clinical specimens. Contrarily, FOXO4 was frequently down-regulated in NSCLC cell lines and clinical specimens. Functional studies show that ectopic expression of miR-150 enhanced tumor cell metastasis in vitro and in a mouse xenograft model, and triggered EMT-like changes in NSCLC cells (including E-cadherin repression, N-cadherin and Vimentin induction, and mesenchymal morphology). Correspondingly, FOXO4 knockdown exhibited pro-metastatic and molecular effects resembling the effect of miR-150 over-expression. Moreover, NF-κB/snail/YY1/RKIP circuitry regulated by FOXO4 were likely involved in miR-150-induced EMT event. Simultaneous knockdown of miR-150 and FOXO4 abolished the phenotypic and molecular effects caused by individual knockdown of miR-150. Therefore, our study provides previously unidentified pro-metastatic roles and mechanisms of miR-150 in NSCLC.

Details

Language :
English
ISSN :
20452322
Database :
OpenAIRE
Journal :
Scientific Reports
Accession number :
edsair.doi.dedup.....bdfdc3b909ba2c6bbe877933043586cf
Full Text :
https://doi.org/10.1038/srep39001