TY - JOUR
T1 - miR-143 Interferes with ERK5 Signaling, and Abrogates Prostate Cancer Progression in Mice
AU - Clape, Cyrielle
AU - Fritz, Vanessa
AU - Henriquet, Corinne
AU - Apparailly, Florence
AU - Fernandez, Pedro Luis
AU - Iborra, Francois
AU - Avances, Christophe
AU - Villalba, Martin
AU - Culine, Stephane
AU - Fajas, Lluis
PY - 2009/10/26
Y1 - 2009/10/26
N2 - Background: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo.Results: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer.Conclusions: miR-143 is as a new target for prostate cancer treatment.
AB - Background: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo.Results: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5) activity. We show here that ERK5 is a miR-143 target in prostate cancer.Conclusions: miR-143 is as a new target for prostate cancer treatment.
KW - ACTIVATED-RECEPTOR-GAMMA
KW - MICRORNA EXPRESSION
KW - PROMOTES ADIPOGENESIS
KW - RADICAL PROSTATECTOMY
KW - INVASION
KW - PATHWAY
KW - AND-145
KW - GROWTH
KW - TUMORS
KW - RISK
U2 - 10.1371/journal.pone.0007542
DO - 10.1371/journal.pone.0007542
M3 - Article
VL - 4
IS - 10
M1 - 7542
ER -
