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

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
Select reference article to upload


Citation:

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.


Lifespan Factors:
  • miR222 microRNA 222
  • miR221 microRNA 221


  • Update (Admin) | Auto-Update

    Comment on This Data Unit