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miR-17* suppresses tumorigenicity of prostate cancer by inhibiting mitochondrial antioxidant enzymes
miR-17* suppresses tumorigenicity of prostate cancer by inhibiting mitochondrial antioxidant enzymes
- Source :
- PLoS ONE, PLoS ONE, Vol 5, Iss 12, p e14356 (2010)
- Publication Year :
- 2010
-
Abstract
- Aberrant micro RNA (miRNA) expression has been implicated in the pathogenesis of cancer. Recent studies have shown that the miR-17-92 cluster is overexpressed in many types of cancer. The oncogenic function of mature miRNAs encoded by the miR-17-92 cluster has been identified from the 5' arm of six precursors. However, the function of the miRNAs produced from the 3' arm of these precursors remains unknown. The present study demonstrates that miR-17* is able to suppress critical primary mitochondrial antioxidant enzymes, such as manganese superoxide dismutase (MnSOD), glutathione peroxidase-2 (GPX2) and thioredoxin reductase-2 (TrxR2). Transfection of miR-17* into prostate cancer PC-3 cells significantly reduces levels of the three antioxidant proteins and activity of the luciferase reporter under the control of miR-17* binding sequences located in the 3'-untranslated regions of the three target genes. Disulfiram (DSF), a dithiolcarbomate drug shown to have an anticancer effect, induces the level of mature miR-17* and cell death in PCa cells, which can be attenuated by transfection of antisense miR-17*. Increasing miR-17* level in PC-3 cells by a Tet-on based conditional expression system markedly suppresses its tumorigencity. These results suggest that miR-17* may suppress tumorigenicity of prostate cancer through inhibition of mitochondrial antioxidant enzymes.
- Subjects :
- Male
GPX2
Thioredoxin Reductase 2
lcsh:Medicine
Mitochondrion
Transfection
Antioxidants
Superoxide dismutase
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Molecular Biology/Translational Regulation
microRNA
Disulfiram
medicine
Pathology
Humans
lcsh:Science
030304 developmental biology
Oncology/Prostate Cancer
0303 health sciences
Glutathione Peroxidase
Multidisciplinary
biology
Superoxide Dismutase
lcsh:R
Cancer
Prostatic Neoplasms
medicine.disease
Molecular biology
3. Good health
Mitochondria
Gene Expression Regulation, Neoplastic
MicroRNAs
Oncology
Cell culture
030220 oncology & carcinogenesis
Multigene Family
biology.protein
Cancer research
lcsh:Q
Carbamates
Thioredoxin
Toluene
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....c147a81b6275f7fdceb04b02dc0d508f