PloS one, 2013-02, Vol.8 (2), p.e56592
2013
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Details
- Autor(en) / Beteiligte
- Titel
- Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer
- Ist Teil von
- PloS one, 2013-02, Vol.8 (2), p.e56592
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen's growth restriction effect on normal prostate tissue.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0056592Titel-ID: cdi_plos_journals_1351357784
- Format
- –
- Schlagworte
- ABCA1 protein, Algorithms, Androgen receptors, Androgens, Androgens - pharmacology, ATP-binding protein, Binding sites, Biology, Blotting, Western, Cancer, Carcinogenesis, Carcinogens, Cell cycle, Cell growth, Cell Line, Tumor, Cell Proliferation - drug effects, Cell survival, Cell Survival - drug effects, Cell Survival - genetics, Chromatin Immunoprecipitation, Critical Pathways, Epidermal growth factor, Genes, Genetic engineering, Genomes, Genomics, Hormones, Humans, Kinases, Laboratories, Life sciences, Male, Medicine, Messenger RNA, Metastasis, MicroRNA, MicroRNAs, MicroRNAs - genetics, miRNA, Models, Theoretical, Molecular modelling, Pathways, Prostate cancer, Prostatic Neoplasms - genetics, Prostatic Neoplasms - metabolism, Proteins, Receptors, Androgen - genetics, Receptors, Androgen - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Signaling, Target recognition