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PMID: 19962668 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation.

Cancer cell ·Vol. 16 ·No. 6 ·2009-12-08 ·Pages 498-509

Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM

Abstract

Lung 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.

MeSH Terms
Carcinoma, Non-Small-Cell Lung/pathology Down-Regulation/physiology Humans Liver Neoplasms/pathology MicroRNAs/physiology PTEN Phosphohydrolase/physiology TNF-Related Apoptosis-Inducing Ligand/physiology Tissue Inhibitor of Metalloproteinase-3/physiology
Chemicals
MIRN221 microRNA, human MIRN222 microRNA, human MicroRNAs TIMP3 protein, human TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Tissue Inhibitor of Metalloproteinase-3 PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Garofalo Michela
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Di Leva Gianpiero
Romano Giulia
Nuovo Gerard
Suh Sung-Suk
Ngankeu Apollinaire
Taccioli Cristian
Pichiorri Flavia
Alder Hansjuerg
Secchiero Paola
Gasparini Pierluigi
Gonelli Arianna
Costinean Stefan
Acunzo Mario
Condorelli Gerolama
Croce Carlo Maria
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2009.10.014
Published
2009-12-08
Pages
498-509
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2796583
Subset
IM
Grants
NCI NIH HHS · R01 CA135030 · United States
NCI NIH HHS · R01 CA135030-01A1 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2009.10.014 PMC Full Text View journal details
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