MiRNA 26a expression in a novel panel of African American prostate cancer cell lines.

INTRODUCTION: African American men have disproportionately high incidence and mortality rates of prostate cancer when compared to other ethnic groups in the United States. The identification of molecular factors that contribute to this disparity could improve diagnosis and therapeutic intervention. Therefore, the purpose of this study was to determine the miRNA 26a expression profile in novel African American and Caucasian prostate cell lines at each clinical stage of prostate cancer progression. METHODS: The miR-26a expression profile was investigated using novel African American and Caucasian prostate cell lines representing each pathological stage: non-malignant, malignant, and metastatic tumors. Relative miRNA expression was determined by qRT-PCR. RESULTS: Our data showed a 2.25 fold increase for miR-26a in the non-malignant, a 13.3 fold increase in malignant and 2.38 fold increase in metastatic tumors, when comparing African American and Caucasian prostate cell lines of similar clinical stage and pathological grade. African American malignant prostate cancer cell lines showed the most significant fold difference in expression among all cell lines tested. Furthermore, there was a general increase in miR-26a expression toward the more aggressive cell lines in both African American and Caucasian prostate cell lines. CONCLUSION: To date, we are unaware of any studies that compare the miRNA profile at different stages of prostate cancer among two racial groups. Although a gene target for miR-26a has not been identified, our data show a possible role for miRNA regulation of gene expression in prostate cancer progression. Furthermore, this study suggests that miRNAs could possibly contribute to the aggressiveness associated in African American patients with prostate cancer.

MicroRNA profiling of novel African American and Caucasian Prostate Cancer cell lines reveals a reciprocal regulatory relationship of miR-152 and DNA methyltranferase 1.

miRNA expression in African American compared to Caucasian PCa patients has not been widely explored. Herein, we probed the miRNA expression profile of novel AA and CA derived prostate cancer cell lines. We found a unique miRNA signature associated with AA cell lines, independent of tumor status. Evaluation of the most differentially expressed miRNAs showed that miR-132, miR-367b, miR-410, and miR-152 were decreased in more aggressive cells, and this was reversed after treatment of the cells with 5-aza-2'-deoxycytidine. Sequencing of the miR-152 promoter confirmed that it was highly methylated. Ectopic expression of miR-152 resulted in decreased growth, migration, and invasion. Informatics analysis of a large patient cohort showed that decreased miR-152 expression correlated with increased metastasis and a decrease in biochemical recurrence free survival. Analysis of 39 prostate cancer tissues with matched controls (20 AA and 19 CA), showed that 50% of AA patients had statistically significant lower miR-152 expression compared to only 35% of CA patients. Ectopic expression of miR-152 in LNCaP, PC-3, and MDA-PCa-2b cells down-regulated DNA (cytosine-5)-methyltransferase 1 (DNMT1) through direct binding in the DNMT1 3'UTR. There appeared to be a reciprocal regulatory relationship of miR-152/DNMT1 expression, as cells treated with siRNA DNMT1 caused miR-152 to be re-expressed in all cell lines. In summary, these results demonstrate that epigenetic regulation of miR-152/DNMT1 may play an important role in multiple events that contribute to the aggressiveness of PCa tumors, with an emphasis on AA PCa patients .