Prostate cancer (PCa) is the most common type of cancer in men in the United States and is expected to result in ∼218,000 new cases and about 32,000 deaths in 2010. Recently, microRNA miR-34a has been associated with many cancers including prostate cancer. It has been shown that tumor suppressor p53 transcriptionally regulates the expression of microRNA- miR-34a, which confers translational inhibition and mRNA degradation of genes involved in cell cycle control and apoptosis. Several GWAS studies have reported that Single nucleotide polymorphisms (SNPs) in microRNA coding genes (both in seed and mature sequence) or their target binding sites may alter the strength of miRNA binding and deregulate target gene expression. To our interest we aimed to explore the effect of germ line polymorphism rs35301225 (A/C/T) residing in miR-34a (rs35301225) on the cell cycle progression and apoptosis. Prostate (PC3 and LnCap) and breast cancer (MDA-MB 231) cell lines were transfected with pre miRNA mimics containing A/C/T alleles (rs35301225) of miR-34a and the expression of CYCLIN D1, CDK4, CDK6 and proteins associated with cellular signaling cascades, involved in cell cycle regulation were determined by Western blotting. Luciferase assay was performed for the target evaluation. The cell proliferation and apoptosis were measured by WST-1 assay and flow cytometry respectively. The expressions of apoptosis-related proteins were detected by Western blotting in the transfected cells. Western blot analysis showed that CYCLIN D1, CDK4, CDK6 and other downstream molecules were significantly down-regulated in the presence of C allele, whereas no such reduction of expression was observed in the presence of A or T allele. Cell proliferation assay showed that different alleles of miR-34a also exert profound effect on proliferation pattern of cells. Flow cytometry analysis also showed that cells with different alleles of miR-34a may exert significant effect on cell cycle progression and apoptosis. To explore if this phenomenon was confined to prostate cancer cell lines or different alleles of mir-34a may alter cell function in general, experiments were repeated with a breast cancer cell line, MDA-MB-231. Interestingly the results obtained in breast cancer cell lines were similar to that obtained in prostate cancer cell lines. The results suggest that genetic variants residing in the mature miRNA may exert a substantial effect on their expression and function, which needs to be explored along with the biological effect of miRNAs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 206. doi:1538-7445.AM2012-206