The MicroRNA Profile of Prostate Carcinoma Obtained by Deep Sequencing

Abstract

Prostate cancer is a leading cause of tumor mortality. To characterize the underlying molecular mechanisms, we have compared the microRNA (miRNA) profile of primary prostate cancers and noncancer prostate tissues using deep sequencing. MiRNAs are small noncoding RNAs of 21 to 25 nucleotides that regulate gene expression through the inhibition of protein synthesis. We find that 33 miRNAs were upregulated or downregulated >1.5-fold. The deregulation of selected miRNAs was confirmed by both Northern blotting and quantitative reverse transcription-PCR in established prostate cancer cell lines and clinical tissue samples. A computational search indicated the 3′-untranslated region (UTR) of the mRNA for myosin VI (MYO6) as a potential target for both miR-143 and miR-145, the expression of which was reduced in the tumor tissues. Upregulation of myosin VI in prostate cancer was previously shown by immunohistochemistry. The level of MYO6 mRNA was significantly induced in all primary tumor tissues compared with the nontumor tissue from the same patient. This finding was matched to the upregulation of myosin VI in established prostate cancer cell lines. In luciferase reporter analysis, we find a significant negative regulatory effect on the MYO6 3′UTR by both miR-143 and miR-145. Mutation of the potential binding sites for miR-143 and miR-145 in the MYO6 3′ UTR resulted in a loss of responsiveness to the corresponding miRNA. Our data indicate that miR-143 and miR-145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer. Mol Cancer Res; 8(4); 529-38. ©2010 AACR.

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

“…27,[37][38][39] Interestingly, our miRNA expression data were highly consistent with those of a previous study, 32 which found that miR-205, miR-222 and miR-31 were underexpressed in PCa. Genome-wide miRNA expression signatures can rapidly and precisely reveal aberrant expression of miRNA in cancers.…”

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

“…A strong downregulation of miR-205 in prostate carcinoma was also observed by Boll and colleagues (17). We again noted reduced levels of miRNAs like miR-143, miR-145, miR-320a, or miR-424 as previously described (5). In comparison with our previous profiling, some miRNAs, such as miR-223, miR-221, or miR-27a, remained unchanged in this analysis.…”

“…The results of the deep sequencing analysis (covering only major miRNA transcripts) are shown in Supplementary Table S3. The relative expression levels of the miRNAs were comparable and also matched the results of our previous study of healthy prostate tissue (5). The profiling of the two pools of nonmalignant prostate tissue yielded comparable results for the samples from the corresponding nonmalignant part of the prostate and healthy prostate tissue obtained after radical cystectomy.…”

“…We found that 33 miRNAs were deregulated more than 1.5-fold in the cancer samples (16 miRNAs upregulated, 17 downregulated; ref. 5; for a recent review on miRNA expression analysis in prostate carcinoma, see refs. 3,6,7).…”

Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

“…Downregulation of let-7b, miR-1, miR-133a, miR-143, miR-145, miR-221 and miR-222 and upregulation of miR-25, miR-93, mir-96, miR-183, miR-182 or miR-301b has been reported in PCa when compared with benign prostate hyperplasia or normal prostate tissue by at least one research group (Volinia et al, 2006;Porkka et al, 2007;Ozen et al, 2008;Tong et al, 2009;Schaefer et al, 2010;Spahn et al, 2010;Szczyrba et al, 2010). In addition, overexpression of miR-96 and reduced expression of miR-221 have been associated with increased risk of biochemical recurrence and aggressive PCa (Schaefer et al, 2010;Spahn et al, 2010).…”