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MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4
- 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.
- Subjects :
- 0301 basic medicine
Male
Lung Neoplasms
Mice, Nude
Vimentin
Cell Cycle Proteins
Biology
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
miR-150
Carcinoma, Non-Small-Cell Lung
medicine
Animals
Humans
RNA, Neoplasm
Neoplasm Metastasis
A549 cell
Gene knockdown
Multidisciplinary
Mesenchymal stem cell
Forkhead Transcription Factors
medicine.disease
Neoplasm Proteins
MicroRNAs
030104 developmental biology
A549 Cells
030220 oncology & carcinogenesis
FOXO4
biology.protein
Cancer research
Ectopic expression
Female
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....bdfdc3b909ba2c6bbe877933043586cf
- Full Text :
- https://doi.org/10.1038/srep39001