Profiling of a panel of radioresistant prostate cancer cells identifies deregulation of key miRNAs.

BACKGROUND

miRNAs are increasingly associated with the aggressive phenotype of prostate tumours. Their ability to control radiobiologically-relevant cellular processes strengthens their potential as novel markers of response to radiation therapy.

PURPOSE

To identify miRNAs associated with increased clonogenic survival following radiation exposure.

MATERIAL AND METHODS

The miRNA expression profiles of a panel of 22RV1 cells with varying levels of radiosensitivities (hypoxic H-22Rv1 cells, RR-22Rv1 cells derived from WT-22Rv1 cells through 2-Gy fractionated repeated exposure, the associated aged matched cells (AMC-22Rv1) and the WT-22Rv1 cell lines) were generated and cross-analysed to identify common miRNAs associated with a radioresistant phenotype.

RESULTS

Increased clonogenic survival following irradiation was associated with significant modifications in miRNA expression pattern. miR-221 (up) and miR-4284 (down) in RR-22Rv1 and MiR-31 and miR-200c in AMC-22Rv1 were the most uniquely significantly deregulated miRNAs when compared to WT-22Rv1 cells. miR-200c ranked as the most downregulated miRNAs in hypoxic, when compared to RR-22Rv1 cells. miR-200a was the only differentially expressed miRNA between RR-22Rv1 and AMC-22Rv1 cells. miR-210 yielded the highest fold change in expression in H-22Rv1, when compared to WT-22RV1 cells.

CONCLUSION

This study identifies candidate miRNAs for the development of novel prognostic biomarkers for radiotherapy prostate cancer patients.