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Widespread deregulation of microRNA expression in human prostate cancer

Abstract

MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression by binding to mRNA sequences and repressing target-gene expression post-transcriptionally, either by inhibiting translation or promoting RNA degradation. We have analysed expression of 328 known and 152 novel human miRNAs in 10 benign peripheral zone tissues and 16 prostate cancer tissues using microarrays and found widespread, but not universal, downregulation of miRNAs in clinically localized prostate cancer relative to benign peripheral zone tissue. These findings have been verified by real-time RT–PCR assays on select miRNAs, including miR-125b, miR-145 and let-7c. The downregulated miRNAs include several with proven target mRNAs whose proteins have been previously shown to be increased in prostate cancer by immunohistochemistry, including RAS, E2F3, BCL-2 and MCL-1. Using a bioinformatics approach, we have identified additional potential mRNA targets of one of the miRNAs, (miR-125b) that are upregulated in prostate cancer and confirmed increased expression of one of these targets, EIF4EBP1, in prostate cancer tissues. Our findings indicate that changes in miRNA expression may have an important role in the biology of human prostate cancer.

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References

  • Barberis MCP, Roz E, Biunno I . (2006). SEL1L expression in prostatic intraepithelial neoplasia and adenocarcinoma: an immunohistochemical study. Histopathology 48: 614–616.

    Article  CAS  Google Scholar 

  • Biunno I, Cattaneo M, Orlandi R, Canton C, Biagiotti L, Ferrero S et al. (2006). SEL1L: a multifaceted protein playing a role in tumor progression. J Cell Physiol 208: 23–38.

    Article  CAS  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D . (1998). Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95: 14863–14868.

    Article  CAS  Google Scholar 

  • Gorgoni B, Gray NK . (2004). The roles of cytoplasmic poly(A)-binding proteins in regulating gene expression: a developmental perspective. Brief Funct Genomic Proteomic 3: 125–141.

    Article  CAS  Google Scholar 

  • Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ . (2006). miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34: D140–D144.

    Article  CAS  Google Scholar 

  • Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65: 7065–7070.

    Article  CAS  Google Scholar 

  • Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A et al. (2005). RAS is regulated by the let-7 microRNA family. Cell 120: 635–647.

    Article  CAS  Google Scholar 

  • Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ et al. (2007). A microRNA signature of hypoxia. Mol Cell Biol 27: 1859–1867.

    Article  CAS  Google Scholar 

  • Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T . (2007). Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39: 673–677.

    Article  CAS  Google Scholar 

  • Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K et al. (2004). Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 101: 811–816.

    Article  CAS  Google Scholar 

  • Liu C-G, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M et al. (2004). An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 101: 9740–9744.

    Article  CAS  Google Scholar 

  • Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. (2005). MicroRNA expression profiles classify human cancers. Nature 435: 834–838.

    Article  CAS  Google Scholar 

  • Marsit CJ, Eddy K, Kelsey KT . (2006). MicroRNA responses to cellular stress. Cancer Res 66: 10843–10848.

    Article  CAS  Google Scholar 

  • Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK et al. (2006). Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer 5: 24.

    Article  Google Scholar 

  • Rojo F, Najera L, Lirola J, Jimenez J, Guzman M, Sabadell MD et al. (2007). 4E-binding protein 1: a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis. Clin Cancer Res 13: 81–89.

    Article  CAS  Google Scholar 

  • Saldanha AJ . (2004). Java Treeview: extensible visualization of microarray data. Bioinformatics 20: 3246–3248.

    Article  CAS  Google Scholar 

  • Shingara J, Keiger K, Shelton J, Laosinchai-Wolf W, Powers P, Conrad R et al. (2005). An optimized isolation and labeling platform for accurate microRNA expression profiling. RNA 11: 1461–1470.

    Article  CAS  Google Scholar 

  • Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103: 2257–2261.

    Article  CAS  Google Scholar 

  • Voorhoeve PM, Agami R . (2006). Classifying microRNAs in cancer: the good, the bad and the ugly. Biochim Biophys Acta 1775: 274–282.

    Google Scholar 

  • Wang JH, Weng JS, Cai Y, Penland R, Liu MY, Ittmann M . (2006). The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase. Prostate 66: 847–857.

    Article  CAS  Google Scholar 

  • Wu W, Sun M, Zou GM, Chen JJ . (2007). MicroRNA and cancer: current status and prospective. Int J Cancer 120: 953–960.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Department of Veterans Affairs Merit Review program (MI) and the National Cancer Institute to the Baylor prostate cancer SPORE program (P50CA058204) and by use of the facilities of the Michael E DeBakey Department of Veterans Affairs Medical Center.

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Correspondence to M Ittmann.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ozen, M., Creighton, C., Ozdemir, M. et al. Widespread deregulation of microRNA expression in human prostate cancer. Oncogene 27, 1788–1793 (2008). https://doi.org/10.1038/sj.onc.1210809

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