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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. 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. miR-143 is as a new target for prostate cancer treatment.

ABSTRACT Purpose The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. Methods We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. Results Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7 %). Most tumors (90.1 %) were organ-confined (pT2), whereas 9.9 % of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9 %), 6 in 575 cases (61.7 %), 7 (3 + 4) in 149 cases (16.0 %), 7 (4 + 3) in 38 cases (4.1 %), and >7 in 40 cases (4.3 %). After a median follow-up of 25.5 months (interquartile range 14.2–47.4), 35.4 % of patients had bladder cancer recurrence and 23.8 % died of bladder cancer. Only 16 patients (1.9 %) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. Conclusions The rate of incidentally diagnosed PCa in RCP specimens was 21.7 %. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9 % of cases during follow-up.

Abstract Network inference aims at unravelling the dependency structure relating jointly observed variables. Graphical models provide a general framework to distinguish between marginal and conditional dependency. Unobserved variables (missing actors) may induce apparent conditional dependencies. In the context of count data, we introduce a mixture of Poisson log-normal distributions with tree-shaped graphical models, to recover the dependency structure, including missing actors. We design a variational EM algorithm and assess its performance on synthetic data. We demonstrate the ability of our approach to recover environmental drivers on two ecological data sets. The corresponding R package is available from github.com/Rmomal/nestor.