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The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers
- Source :
- Oncogene
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Metastatic lung cancer is one of the most lethal forms of cancer and molecular pathways driving metastasis are still not clearly elucidated. Metastatic cancer cells undergo an epithelial-mesenchymal transition (EMT) where they lose their epithelial properties and acquire a migratory and invasive phenotype. Here we identify that expression of microRNAs from the miR-200 family and the miR-183~96~182 cluster are significantly co-repressed in non-small cell lung cancer (NSCLC) cell lines and primary tumors from multiple TCGA data sets with high EMT scores. Ectopic expression of the miR-183~96~182 cluster inhibited cancer cell migration and invasion, while its expression was tightly modulated by miR-200. We identified Foxf2 as a common, novel and direct target of both these microRNA families. Foxf2 expression tightly correlates with the transcription factor Zeb1 and is elevated in mesenchymal-like metastatic lung cancer cells. Foxf2 expression induced robust EMT, migration, invasion and metastasis in lung cancer cells, whereas Foxf2 inhibition significantly repressed these phenotypes. We also demonstrated that Foxf2 transcriptionally represses E-Cadherin and miR-200, independent of Zeb1, to form a double negative feedback loop. We therefore identified a novel mechanism whereby the miR-200 family and the miR-183~96~182 cluster inhibit lung cancer invasion and metastasis by targeting Foxf2.
- Subjects :
- 0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Lung Neoplasms
Mice, Inbred Strains
Biology
Article
Metastasis
03 medical and health sciences
Cell Movement
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
microRNA
Genetics
medicine
Animals
Humans
Epithelial–mesenchymal transition
Lung cancer
Molecular Biology
Zeb1
Homeodomain Proteins
Regulation of gene expression
EMT
Zinc Finger E-box-Binding Homeobox 1
Cancer
Forkhead Transcription Factors
miR-200
invasion
Cadherins
medicine.disease
Xenograft Model Antitumor Assays
Foxf2
3. Good health
Gene Expression Regulation, Neoplastic
lung cancer
MicroRNAs
030104 developmental biology
Multigene Family
Immunology
Cancer cell
Cancer research
Ectopic expression
miR-183-96-182
Transcription Factors
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....7cf19a4541317e8fea8e1864053e94ad