miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice.
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.
Clapé
Cyrielle
C
Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.
Fritz
Vanessa
V
Henriquet
Corinne
C
Apparailly
Florence
F
Fernandez
Pedro Luis
PL
Iborra
François
F
Avancès
Christophe
C
Villalba
Martin
M
Culine
Stéphane
S
Fajas
Lluis
L
D000818:Animals; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D018450:Disease Progression; D018274:Electroporation; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
C542359:MIRN143 microRNA, human; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D048054:Mitogen-Activated Protein Kinase 7