Validation of differential expression of microRNA profiles in prostate cancer specimens.

Abstract

203 Background: MicroRNAs (miRNA) are small, noncoding nucleic acids that regulate expression of genes. Altered expression of miRNA has been implicated as a factor in carcinogenesis. We previously demonstrated 27 miRNA with differential expression that varied greater than two-fold between areas of benign and cancerous prostate glands in 64 patients. The goal of this study was to validate these findings in a selected group. Methods: RNA was extracted from prostate cancer foci and areas of benign glands from paraffin embedded prostatectomy specimens from 29 selected patients. Five patients each were selected with Gleason 3+3, 3+4, 4+3, and 4+4 or higher. The remaining nine selected patients went on to develop metastatic disease. Expression profiles for 577 miRNA were analyzed using Taqman OpenArray. Data analysis was performed using the mean-centering method for normalizing miRNA across the original and validation cohorts. Results: Significant overlap was found between the original and validation cohorts for miRNA that were upregulated at least two-fold between benign and cancerous glands (p<0.05). There were no differences in miRNA expression between T2 and T3 cases. Comparison of Gleason 6 vs Gleason 8+ showed significant difference in expression of mir-185, mir106b, and mir-181a. Interestingly, among the subset of patients that developed metastatic disease, the benign prostate glands demonstrated significant overexpression of mir-21 as compared to the benign glands of the localized cohort. Mir-21 is a known oncomir shown to be overexpressed in other metastatic tumors. Conclusions: This study validates our findings on differential expression of miRNA between cancerous and benign glands. There was a significant difference in expression of three miRNAs between Gleason 6 and 8 cancers, and no differences were found between T2 and T3. miRNA may represent a unique signature in the benign glands of patients with metastatic disease.

Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage

“…MiRNAs are characterized by variable expression in cells and tissues, which is influenced by the molecular cell environment. Differential expression of miRNAs has been shown associated with cancer-related diseases 15 , 16 , cardiovascular diseases 17 , 18 , and neurological conditions 19 , 20 . In addition, miRNAs are more resistant to degradation than mRNA and can be detected in fresh, fixed, or frozen tissue and peripheral blood samples.…”