Authors: 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.
Keywords: 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
Journal: Cancer cell Volume: 16 Issue: 6 Pages: 498-509 Date: Dec. 8, 2009 PMID: 19962668 |
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 (2009) miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer cell 16: 498-509.
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