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| Status |
Public on Dec 01, 2011 |
| Title |
MicroRNA-1 is a candidate tumor suppressor and prognostic marker |
| Platform organisms |
Homo sapiens; Mus musculus |
| Sample organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Non-coding RNA profiling by array
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| Summary |
MicroRNAs (miRs) are small non-coding RNAs that can function as tumor suppressor genes. 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 dataset and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the candidate tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer cells. 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 miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters gH2A.X marker expression and affects the cellular organization of F-actin 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.
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| Overall design |
In this study we monitored global miRNA expression changes in prostate cancer LNCaP cells treated with the epigenetic compounds 5-Azacytidine (5-AzaC) and/or trichostatin A (TSA). Cells were treated with epigenetic drugs for 36 hours and total RNA was isolated for hybridization to miRNA microarrays. 5 independent experiments were performed (n=4 for combined treatment).
The candidate prostate tumor suppressor miRNAs, miR-1, miR-206, and miR-27 were up-regulated in LNCaP cells for Affymetrix microarray analysis. LNCaP cells were transfected with pre-miR oligos and 24 hr post-transfection total RNA was collected for microarray analysis; total of three independent experiments.
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| Contributor(s) |
Hudson RS, Ambs S, Yi M |
| Citation(s) |
22210864, 23409773 |
| |
| Submission date |
Aug 23, 2011 |
| Last update date |
Sep 17, 2019 |
| Contact name |
Robert Scott Hudson |
| Organization name |
NIH
|
| Department |
NCI
|
| Lab |
The Laboratory of Human Carcinogenesis
|
| Street address |
National Cancer Institute Room Blgd.37/3044
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20852 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
| GPL14184 |
OSU-CCC Human and Mouse MicroRNA Microarray Version 4.0 |
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| Samples (34)
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| Relations |
| BioProject |
PRJNA145531 |
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