miR-205 exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase C epsilon
Articolo
Data di Pubblicazione:
2009
Citazione:
miR-205 exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase C epsilon / P. Gandellini, M. Folini, N. Longoni, M. Pennati, M. Binda, M. Colecchia, R. Salvioni, R. Supino, R.M. Moretti, P. Limonta, R. Valdagni, M.G. Daidone, N. Zaffaroni. - In: CANCER RESEARCH. - ISSN 0008-5472. - 69:6(2009 Mar 15), pp. 2287-2295. [10.1158/0008-5472.CAN-08-2894]
Abstract:
Abstract
Limited information is available concerning the expression
and role of microRNAs in prostate cancer. In this study, we
investigated the involvement of miR-205 in prostate carcinogenesis.
Significantly lower miR-205 expression levels were
found in cancer than in normal prostate cell lines as well
as in tumor compared with matched normal prostate tissues,
with a particularly pronounced reduction in carcinomas from
patients with local-regionally disseminated disease. Restoring
the expression of miR-205 in prostate cancer cells resulted
in cell rearrangements consistent with a mesenchymalto-
epithelial transition, such as up-regulation of E-cadherin
and reduction of cell locomotion and invasion, and in the
down-regulation of several oncogenes known to be involved
in disease progression (i.e., interleukin 6, caveolin-1, EZH2).
Our evidence suggests that these events are driven by the
concurrent repression of specific predicted miR-205 targets,
namely N-chimaerin, ErbB3, E2F1, E2F5, ZEB2, and protein
kinase CE. Strikingly, the latter seemed to play a direct role
in regulating epithelial-to-mesenchymal transition. In fact, its
down-regulation led to a cell phenotype largely reminiscent
of that of cells ectopically expressing miR-205. Overall,
we showed for the first time that miR-205 exerts a tumorsuppressive
effect in human prostate by counteracting
epithelial-to-mesenchymal transition and reducing cell
migration/invasion, at least in part through the downregulation
of protein kinase CE. [Cancer Res 2009;69(6):2287–95]
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Gandellini, M. Folini, N. Longoni, M. Pennati, M. Binda, M. Colecchia, R. Salvioni, R. Supino, R.M. Moretti, P. Limonta, R. Valdagni, M.G. Daidone, N. Zaffaroni
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