MicroRNAs and zinc metabolism-related gene expression in prostate cancer cell lines treated with zinc(II) ions

MicroRNAs (miRNAs) are a large class of single-stranded RNA molecules involvedin post-transcriptional gene silencing. miRNAs not only regulate various developmentaland physiological processes but also are involved in cancer development. Additionally,they can be considered as biomarkers of some pathological processes. The aim ofthis study was to determine the expression levels of selected miRNA and zinc(II)-relatedgenes (ZIP-1, BAX, MT2A and MT1A) in the non-tumor PNT1A prostate cell line incomparison with the prostate cancer cell lines 22Rv1, PC-3 and LNCaP after zinc(II)treatment. Using bioinformatic approaches we selected miRNAs with putative bindingsites in the 3'UTR regions in Metallothionein 1A and 2A as miRNA 23a, 141, 224,296-3p, 320, 375 and 376. We observed significantly higher expression of miRNA 23ain all tumor lines compared to non-tumor PNT1A (13.6-fold in 22Rv1, 7.3-fold inPC-3, 8.3-fold in LNCaP, p<0.01). We also observed that the 22Rv1 cell linehas significantly higher expression of miRNA 224 in comparison to other cell lines.In addition, all tumor cell lines expressed significantly higher levels of miRNA 375in comparison to non-tumor PNT1A (87.1‑fold in 22Rv1, nearly 2,000-fold in PC-3,56.3‑fold in LNCaP, p<0.01). Nevertheless, miRNA 375 and 23a expression levelsstrongly suggest their potential to contribute to the diagnosis of prostate cancerand miRNA 224 eventually may be suitable for classification of primary tumors.The expression of miRNA 224 in 22Rv1 cell line was negatively correlated withincreasing zinc(II) concentration only. Our experiments revealed significant negativecorrelation of miRNA 376 and MT2A in 22Rv1 and a negative correlation betweenmiRNA 224 and MT1A in PC-3 cells which may denote possible direct regulation ofMT genes by specific miRNAs in prostate cancer.