Radiation modulation of microRNA in prostate cancer cell lines.

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.

• Authors: Sajni Josson, Shian-Ying Sung, Kaiqin Lao, Leland W K Chung, Peter A S Johnstone
• Journal: The Prostate (Prostate) Vol. 68 Issue 15 Pg. 1599-606 (Nov 01 2008) ISSN: 1097-0045 [Electronic] United States
• PMID: 18668526 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• ERCC8 protein, human
• MIRN521 microRNA, human
• MicroRNAs
• Transcription Factors
• Superoxide Dismutase
• DNA Repair Enzymes

Topics

• Cell Line, Tumor (drug effects, metabolism, radiation effects)
• DNA Repair Enzymes (metabolism)
• Down-Regulation
• Humans
• Male
• MicroRNAs (metabolism, pharmacology)
• Prostatic Neoplasms (genetics, pathology)
• Radiation Tolerance
• Superoxide Dismutase (metabolism)
• Transcription Factors (metabolism)
• Up-Regulation