Abstract
BackgroundMicro 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.ResultsExpression 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.ConclusionsmiR-143 is as a new target for prostate cancer treatment.
Highlights
Prostate cancer (CaP) is the most frequent cancer and the second leading cause of cancer death in men in western countries
MiRNAs are small, non-coding, single-stranded RNAs of,22 nucleotides that negatively regulate gene expression at the posttranscriptional level, primarily through base pairing to the 39 untranslated region (UTR) of target mRNAs
50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites [8] and some of them have been shown to be directly involved in cancer development and progression [9]
Summary
Prostate cancer (CaP) is the most frequent cancer and the second leading cause of cancer death in men in western countries. Prostate cancer is initially dependent on androgens for growth, and androgen ablation therapy causes regression of the tumor [1], likely through inactivation of the transcription of the AR target genes. Multiple microRNAs have been shown to have oncogenic properties or act like tumor suppressor genes [9,11] This is the case for miR-15A and miR-16-1, which expression is lost in advanced prostate cancer. Most interestingly is the observation that some miRNA, such as miR-141 are secreted by cancer cells, PLoS ONE | www.plosone.org miR-143 and Prostate Cancer and are found in serum of prostate cancer patients These results establish the measurement of tumor-derived miRNAs in serum or plasma as a novel diagnostic tool for a non-invasive method of detection of human cancer [15]. 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
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