MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer.
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.
Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA.
Robert S
RS
Hudson
Ming
M
Yi
Dominic
D
Esposito
Stephanie K
SK
Watkins
Arthur A
AA
Hurwitz
Harris G
HG
Yfantis
Dong H
DH
Lee
James F
JF
Borin
Michael J
MJ
Naslund
Richard B
RB
Alexander
Tiffany H
TH
Dorsey
Robert M
RM
Stephens
Carlo M
CM
Croce
Stefan
S
Ambs
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004260:DNA Repair / Q000235:genetics; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; C544547:MIRN1 microRNA, human; D035683:MicroRNAs