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.
miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice
Clape, C.; Fritz, V.; Henriquet, C.; Apparailly, F.; Fernandez, P. L.; Iborra, F.; Avances, C.; Villalba, M.; Culine, S.; Fajas, L.
2009 / vol 4 / pages e7542
1932-6203 (Electronic) 1932-6203 (Linking)
Cell Line, Tumor; Humans; Animals; Mice; Male; *Signal Transduction; Computational Biology/methods; Disease Progression; Mice, Nude; Electroporation; In Situ Hybridization; MicroRNAs/*metabolism; Mitogen-Activated Protein Kinase 7/*metabolism; Prostatic Neoplasms/*metabolism