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miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation
- Source :
- Cancer Cell
- Publication Year :
- 2009
-
Abstract
- SummaryLung and liver cancers are among the most deadly types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor, underlining the need for development of targeted therapies. MicroRNAs represent a class of small RNAs frequently deregulated in human malignancies. We now report that miR-221&222 are overexpressed in aggressive non-small cell lung cancer and hepatocarcinoma cells, as compared with less invasive and/or normal lung and liver cells. We show that miR-221&222, by targeting PTEN and TIMP3 tumor suppressors, induce TRAIL resistance and enhance cellular migration through the activation of the AKT pathway and metallopeptidases. Finally, we demonstrate that the MET oncogene is involved in miR-221&222 activation through the c-Jun transcription factor.
- Subjects :
- Cancer Research
C-Met
Down-Regulation
TRAIL
CELLCYCLE
Biology
Bioinformatics
Article
TNF-Related Apoptosis-Inducing Ligand
chemistry.chemical_compound
Downregulation and upregulation
Carcinoma, Non-Small-Cell Lung
microRNA
medicine
PTEN
Humans
lung and liver cancers
PI3K/AKT/mTOR pathway
Tissue Inhibitor of Metalloproteinase-3
Liver Neoplasms
PTEN Phosphohydrolase
Cancer
Cell migration
Cell Biology
Cell cycle
medicine.disease
MicroRNAs
chemistry
Oncology
Cancer research
biology.protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....4d9739abddb750070e2759db46b9a6e6