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MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer

Prostate cancer is a major hormone-dependent tumor affecting men, and is often treated by hormone therapy at the primary stages. Despite its initial efficiency, the disease eventually acquires resistance, resulting in the recurrence of castration-resistant prostate cancer. Recent studies suggest tha...

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Autores principales: Miyazaki, Toshiaki, Ikeda, Kazuhiro, Sato, Wataru, Horie-Inoue, Kuniko, Okamoto, Koji, Inoue, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626659/
https://www.ncbi.nlm.nih.gov/pubmed/26506397
http://dx.doi.org/10.3390/jcm4101853
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author Miyazaki, Toshiaki
Ikeda, Kazuhiro
Sato, Wataru
Horie-Inoue, Kuniko
Okamoto, Koji
Inoue, Satoshi
author_facet Miyazaki, Toshiaki
Ikeda, Kazuhiro
Sato, Wataru
Horie-Inoue, Kuniko
Okamoto, Koji
Inoue, Satoshi
author_sort Miyazaki, Toshiaki
collection PubMed
description Prostate cancer is a major hormone-dependent tumor affecting men, and is often treated by hormone therapy at the primary stages. Despite its initial efficiency, the disease eventually acquires resistance, resulting in the recurrence of castration-resistant prostate cancer. Recent studies suggest that dysregulation of microRNA (miRNA) function is one of the mechanisms underlying hormone therapy resistance. Identification of critical miRNAs involved in endocrine resistance will therefore be important for developing therapeutic targets for prostate cancer. In the present study, we performed an miRNA library screening to identify anti-androgen bicalutamide resistance-related miRNAs in prostate cancer LNCaP cells. Cells were infected with a lentiviral miRNA library and subsequently maintained in media containing either bicalutamide or vehicle for a month. Microarray analysis determined the amounts of individual miRNA precursors and identified 2 retained miRNAs after one-month bicalutamide treatment. Of these, we further characterized miR-216a, because its function in prostate cancer remains unknown. miR-216a could be induced by dihydrotestosterone in LNCaP cells and ectopic expression of miR-216a inhibited bicalutamide-mediated growth suppression of LNCaP cells. Furthermore, a microarray dataset revealed that the expression levels of miR-216a were significantly higher in clinical prostate cancer than in benign samples. These results suggest that functional screening using an miRNA expression library could be useful for identifying novel miRNAs that contribute to bicalutamide resistance in prostate cancer.
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spelling pubmed-46266592015-11-12 MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer Miyazaki, Toshiaki Ikeda, Kazuhiro Sato, Wataru Horie-Inoue, Kuniko Okamoto, Koji Inoue, Satoshi J Clin Med Article Prostate cancer is a major hormone-dependent tumor affecting men, and is often treated by hormone therapy at the primary stages. Despite its initial efficiency, the disease eventually acquires resistance, resulting in the recurrence of castration-resistant prostate cancer. Recent studies suggest that dysregulation of microRNA (miRNA) function is one of the mechanisms underlying hormone therapy resistance. Identification of critical miRNAs involved in endocrine resistance will therefore be important for developing therapeutic targets for prostate cancer. In the present study, we performed an miRNA library screening to identify anti-androgen bicalutamide resistance-related miRNAs in prostate cancer LNCaP cells. Cells were infected with a lentiviral miRNA library and subsequently maintained in media containing either bicalutamide or vehicle for a month. Microarray analysis determined the amounts of individual miRNA precursors and identified 2 retained miRNAs after one-month bicalutamide treatment. Of these, we further characterized miR-216a, because its function in prostate cancer remains unknown. miR-216a could be induced by dihydrotestosterone in LNCaP cells and ectopic expression of miR-216a inhibited bicalutamide-mediated growth suppression of LNCaP cells. Furthermore, a microarray dataset revealed that the expression levels of miR-216a were significantly higher in clinical prostate cancer than in benign samples. These results suggest that functional screening using an miRNA expression library could be useful for identifying novel miRNAs that contribute to bicalutamide resistance in prostate cancer. MDPI 2015-10-20 /pmc/articles/PMC4626659/ /pubmed/26506397 http://dx.doi.org/10.3390/jcm4101853 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Miyazaki, Toshiaki
Ikeda, Kazuhiro
Sato, Wataru
Horie-Inoue, Kuniko
Okamoto, Koji
Inoue, Satoshi
MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title_full MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title_fullStr MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title_full_unstemmed MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title_short MicroRNA Library-Based Functional Screening Identified Androgen-Sensitive miR-216a as a Player in Bicalutamide Resistance in Prostate Cancer
title_sort microrna library-based functional screening identified androgen-sensitive mir-216a as a player in bicalutamide resistance in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626659/
https://www.ncbi.nlm.nih.gov/pubmed/26506397
http://dx.doi.org/10.3390/jcm4101853
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