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Br J Cancer. 2017 Jul 25;117(3):409-420. doi: 10.1038/bjc.2017.191. Epub 2017 Jun 22.

Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer.

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
2
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
3
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
4
Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Japan.
5
Department of Pathology, Teikyo University Chiba Medical Center, Ichihara, Japan.

Abstract

BACKGROUND:

Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed.

METHODS:

Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa).

RESULTS:

Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa.

CONCLUSIONS:

Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.

PMID:
28641312
PMCID:
PMC5537499
DOI:
10.1038/bjc.2017.191
[Indexed for MEDLINE]
Free PMC Article

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