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Prostate. 2008 Nov 1;68(15):1599-606. doi: 10.1002/pros.20827.

Radiation modulation of microRNA in prostate cancer cell lines.

Author information

1
Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA. sjosson@emory.edu

Abstract

BACKGROUND:

MicroRNAs (miRNA) are gene regulators and play an important role in response to cellular stress.

METHODS:

Using multiplexed quantitative real-time PCR we performed global miRNA screening of prostate cancer cells in response to radiation treatment.

RESULTS:

Several miRNA were significantly altered in response to radiation treatment. Significant changes were observed in miR-521 and miR-34c. To determine the role of miR-521 in radiation response we transiently overexpressed miR-521 using miR-521 mimic. The miR-521 mimic significantly sensitized prostate cancer cells to radiation treatment. Conversely, ectopic inhibition of miR-521 resulted in radiation resistance of prostate cancer cells. To determine the mechanism by which miR-521 modulates radiation sensitivity we measured the expression levels of one of its predicted target protein, Cockayne syndrome protein A (CSA). CSA is a DNA repair protein, and its levels correlated inversely with the levels of miR-521. Radiation treatment downregulated the levels of miR-521 and upregulated CSA protein. Similarly, ectopic inhibition of miR-521 resulted in increased CSA protein levels. Therefore by altering the levels of CSA protein, miR-521 sensitized prostate cancer cells to radiation treatment.

CONCLUSION:

miR-521 modulates the expression levels of DNA repair protein, CSA and plays an important role, in the radio-sensitivity of prostate cancer cell lines. Thus miR-521 can be a potential target for enhancing the effect of radiation treatment on prostate cancer cells.

PMID:
18668526
PMCID:
PMC3182144
DOI:
10.1002/pros.20827
[Indexed for MEDLINE]
Free PMC Article

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