The expression levels of microRNAs that have the androgen receptor in localized prostate cancer as a target.

Abstract

206 Background: Prostate cancer (PC) depends on the androgen activity being the androgen blockage the main treatment in the setting of metastatic disease. Mechanisms of resistance in metastatic tumors are not completely known. MicroRNAs (miRNA) are small non-coding molecules that have as canonical mechanism the negative control of gene expression promoting messenger RNA (mRNA) degradation or impairing protein translation. The role of miRNAs that have as target the AR are still unknown. Our objective is to study the expression profile of miRNAs that have AR as target in localized prostate cancer. Methods: The expression levels of miRNAs that have as target AR (miR9, 34a, 34c, 185, 130a, 299, 421, 371, 541) were studied using qRT-PCR in the surgical specimens of 83 patients that underwent radical prostatectomy to treat localized prostate cancer. The expression levels of miRNAs were correlated to Gleason score (GS), pre-operatory PSA, pathological stage and biochemical recurrence (PSA>0.2 ng/mL) in a mean follow up of 45.9 months. The mean age was 62.9, mean GS was 7.2, mean PSA was 7.93 ng/mL, and 42 (50.6%) patients were staged pT2. Twenty-four (28.9%) patients presented biochemical recurrence. Specimens of six patients submitted to open surgery to treat benign prostate hyperplasia (BPH) composed the control group. Results: The mean expression of AR was 1.63, being overexpressed in 59% of the cases. The mean expression levels of the nine studied miRNAs was miR9=3.06, miR34a=0.76, miR34c=1.14, miR185=1.65, miR130a=1.9, miR299=6.23, miR421=2.84, miR371=1.41, and miR541=0.93. The univariate analysis showed that pT2 tumors have higher expression of miR371(p=0.009). Conclusions: In localized PC the higher expression of miR371 is related with organ-confined disease. This miRNA could be important in the control of AR and the comprehension of its role in PC might bring alternatives to treat metastatic disease. Funded by FAPESP – 2012/50163-0.