1. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation
- Author
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Pierluigi Gasparini, Paola Secchiero, Giulia Romano, Gianpiero Di Leva, Cristian Taccioli, Hansjuerg Alder, Flavia Pichiorri, Carlo M. Croce, Michela Garofalo, Mario Acunzo, Arianna Gonelli, Apollinaire Ngankeu, Gerard J. Nuovo, Gerolama Condorelli, Sung-Suk Suh, Stefan Costinean, Garofalo, M., Di Leva, G., Romano, G., Nuovo, G, Suh, S. S., Ngankeu, A., Taccioli, C., Pichiorri, F., Alder, H., Secchiero, P., Gasparini, P., Gonelli, A., Costinean, S., Acunzo, M., Condorelli, Gerolama, and Croce, C. M.
- 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 - 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.
- Published
- 2009