let-7a and its target, insulin-like growth factor 1 receptor, are differentially expressed in recurrent prostate cancer

Abstract

Prostate cancer (PCa) is the most common malignancy in males worldwide. Approximately 30% of those patients who received radical prostatectomy developed clinical recurrence accompanied by elevated serum prostate-specific antigen levels. Although knowledge regarding the development of PCa has been significantly improved, the molecular mechanism underlying recurrence remains largely unknown. The objective of the present study was to identify the differentially expressed microRNAs (miRNAs) in recurrent PCa to explore the possible involvement of miRNAs in the relapse. The expression of 6 miRs that have been previously reported to be downregulated in PCa stem cells were examined in a total of 32 recurrent and 36 non-recurrent PCa samples, and let-7a was substantially decreased in the recurrent PCa. Using the online prediction tools, let-7a was identified to virtually target insulin-like growth factor 1 receptor (IGF1R). IGF1R as a target of let-7a was subsequently validated using the luciferase assay. Exogenous expression of let-7a suppressed the expression of IGF1R, and reduced the proliferation of PCa cells by introducing apoptosis to the cells. In conclusion, the present data demonstrated a possible involvement of let-7a in the pathogenesis of recurrent PCa, and it may be a potential target of the disease.