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Activin A regulates microRNAs and gene expression in LNCaP cells
Author(s) -
Ottley Edward Christopher,
Nicholson Helen Diana,
Gold Elspeth Joan
Publication year - 2016
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23184
Subject(s) - lncap , microrna , prostate cancer , biology , cancer research , carcinogenesis , gene expression , transforming growth factor , gene expression profiling , gene , endocrinology , cancer , genetics
BACKGROUND Prostate cancer (PCa) is an increasing health issue worldwide. For patients with advanced castration‐resistant PCa (CRPC) treatment options are limited and overall survival is relatively short. Paired with this, non‐invasive diagnostic options are yet to be established. Activins are members of the TGF‐β superfamily and have been linked to prostate physiology. For instance, activin A is an inhibitor of growth in the prostate. A novel class of non‐coding RNA, microRNAs (miRNAs) have been intrinsically linked to a range of cellular processes and carcinogenesis. No studies have investigated the impact of activin A on miRNA expression in PCa cell lines. Hence, the objective of this study was to determine the effect of activin A on miRNA expression and downstream target genes in PCa. METHODS Activin‐sensitive (LNCaP) and insensitive (PC3) prostate cells were treated with 50 ng/ml of activin A for 72 hr. To examine miRNA expression following treatment, SYBR RT‐qPCR miRNA arrays were used in conjunction with TaqMan RT‐qPCR. MiRPath‐TarBase analysis was conducted using the miRNAs that were significantly altered following activin A treatment of LNCaP cells to highlight enriched target genes within biological pathways. Highlighted target genes were assessed using pathway‐focused TGF‐β and cell cycle SYBR RT‐qPCR arrays. RESULTS Activin A treatment altered nine miRNAs in LNCaP cells: miR‐222‐3p, miR‐15b‐5p, miR‐93‐5p, miR‐18a‐5p, and let‐7i‐5p were significantly decreased, while miR‐30a/30d‐5p, let‐7c, and miR‐196b‐5p were significantly increased versus media control. In PC3 cells five miRNAs were altered: miR‐130a‐3p, miR‐7‐5p, and miR‐140‐3p were significantly decreased while miR‐191‐5p and miR‐26a‐5p were significantly increased versus media control. MiRPath‐TarBase analysis highlighted that the miRNAs significantly altered in LNCaP cells targeted genes contained in activin A‐related KEGG pathways. Furthermore, when LNCaP cells were treated with activin A the expression of the targeted genes was the inverse of the expression of activin A‐mediated miRNAs. CONCLUSIONS This study demonstrated the ability of activin A to modulate miRNA expression in PCa cell lines and suggests a correlative relationship between miRNA expression and downstream target genes in LNCaP cells. This study provides impetus for further studies into activin A and miRNAs in PCa. Prostate 76:951–963, 2016 . © 2016 Wiley Periodicals, Inc.