Final Activity Report Summary - MIRNAPROSTATECANCER (MicroRNA in development and progression of prostate cancer)
Using in silico analyses miR-16 was predicted to target the transcription factor E2F3 that is involved in cell cycle regulation, and has been shown to induce increased proliferation in prostate cancer cells5. It is also a prostate cancer marker, upregulated in 68% of prostate cancers, and correlated with poor survival. The project confirmed that miR-16 has a regulatory effect on E2F3 in vitro; the E2F3 levels are abolished when ectopically expressing miR-16, and when blocking miR-16 in Du145 the E2F3 levels increase with 240%. The Luciferase assay showed that miR-16 binds to the E2F3 3'utr, and that it is corresponding to increased levels of miR-16. Previously, we have found that the over expression of E2F3 protein in prostate cancer cannot been linked to DNA amplification of the E2F3 encoding gene or mRNA over expression, indicating that the deregulation of E2F3 might be caused by miRNAs. The protein levels of E2F3 in different prostate cell lines show an almost perfect negative correlation to the level of miR-16 detected by qRT-PCR Taqman. Hence, these results nicely ties in with this theory.