1. ¹Department of Pathology, Baylor College of Medicine, Houston, TX, USA
2. ²Michael E DeBakey Department of Veterans Affairs Medical Center, Houston, TX, USA
3. ³Department of Medicine, Baylor College of Medicine, Houston, TX, USA
4. ⁴Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

Correspondence: Dr M Ittmann, Department of Pathology, Baylor College of Medicine, One Baylor Plaza Houston, TX 77030, USA. E-mail: mittmann@bcm.tmc.edu

⁵Current address: Yeditepe University, Department of Medical Genetics, Istanbul, Turkey

Received 4 June 2007; Revised 31 July 2007; Accepted 14 August 2007; Published online 24 September 2007.

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.