Abstract 2061: Vitamin D-regulates microRNAs in primary cultures of normal prostatic epithelial cells

Abstract

Abstract Recent discoveries in cancer find that endogenous non-coding RNAs, microRNAs (miRNA), bind to the 3’ untranslated region of target mRNAs and function to translationally repress or decrease mRNA stability. Additionally, a number of studies show that aberrant miRNA expression is linked to various cancers, such as prostate cancer. Cancer-related changes in miRNA levels may result in either repression of tumor suppressor genes and/or activation of oncogenes. MiRNAs pose a potential role as targets in the treatment of cancers. In prostate cancer research, studies suggest a role of vitamin D as a chemopreventive agent. Vitamin D inhibits the growth and differentiation of malignant prostate cells and tumors. Studies show that a reduction in serum levels of vitamin D metabolites is linked to PC occurrence. Research from our laboratory shows that vitamin D treatment alters mRNA stability. This suggests a potential role for miRNAs in the vitamin D prevention of prostate cancer. We hypothesize that vitamin D's prevention of prostate cancer involves up-regulating tumor suppressive miRNAs and down-regulating oncogenic miRNAs. Using normal human prostatic epithelial cells as a model, we investigated the miRNA expression profile changes in cells that were treated with 1,25-dihydroxyvitamin D for time points ranging from 30 min to 24 hours. Our results demonstrated that approximately 50% of the miRNAs are expressed in the normal epithelial cells. A smaller percentage of miRNAs, approximately 10%, were changed by vitamin D treatment. We found that vitamin D down-regulated a small number of miRNAs (<0.5 fold) commonly up-regulated in cancer (miR-181d, miR-378) and up-regulated miRNAs that are down-regulated in cancer (miR-29a, miR-16). Of the miRNAs altered by vitamin D, we observed an interesting down-regulation of the let-7 family of tumor suppressor miRNAs. Six of the seven let-7 family members present on the array (let-7 a-g) were down-regulated across the time points with four of the let-7 miRNAs downregulated as early as 30 minutes. This is a somewhat discrepant finding since let-7 is known as a tumor suppressor miRNA that is decreased in many cancers and we know that vitamin D is a cancer preventive agent. Further studies will determine the role of vitamin D on let-7 in the prostatic epithelial cells and the implications in cancer. Ongoing research will also determine the mechanism of vitamin D regulation of miRNAs to help further understand the chemopreventive role of vitamin D in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2061.