MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer Journal Article

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Authors: Hudson, R. S.; Yi, M.; Esposito, D.; Watkins, S. K.; Hurwitz, A. A.; Yfantis, H. G.; Lee, D. H.; Borin, J. F.; Naslund, M. J.; Alexander, R. B.; Dorsey, T. H.; Stephens, R. M.; Croce, C. M.; Ambs, S
Article Title: MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer
Abstract: We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3'-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.
Journal Title: Nucleic acids research
Volume: 40
Issue: 8
ISSN: 1362-4962; 0305-1048
Publisher: Unknown  
Journal Place: England
Date Published: 2012
Start Page: 3689
End Page: 3703
Language: eng
DOI/URL:

10.1093/nar/gkr1222

10.1093/nar/gkr1222
Notes: LR: 20130626; GEO/GSE31620; GR: U01 CA152758/CA/NCI NIH HHS/United States; JID: 0411011; 0 (Histone Deacetylase Inhibitors); 0 (MIRN1 microRNA, human); 0 (MicroRNAs); 0 (Tumor Markers, Biological); OID: NLM: PMC3333883; 2011/12/30 [aheadofprint]; ppublish