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

Hlavna,Marian; Raudenska,Martina; Hudcova,Kristyna; Gumulec,Jaromir; Sztalmachova,Marketa; Tanhäuserova,Veronika; Babula,Petr; Adam,Vojtech; Eckschlager,Tomas; Kizek,Rene; Masarik,Michal

doi:10.3892/ijo.2012.1655

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

Authors:
- Marian Hlavna
- Martina Raudenska
- Kristyna Hudcova
- Jaromir Gumulec
- Marketa Sztalmachova
- Veronika Tanhäuserova
- Petr Babula
- Vojtech Adam
- Tomas Eckschlager
- Rene Kizek
- Michal Masarik
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Affiliations: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, CZ-625 00 Brno, Czech Republic, Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, CZ-612 42 Brno, Czech Republic, Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol/V Uvalu 84, CZ-150 06 Prague 5, Czech Republic
Published online on: October 9, 2012 https://doi.org/10.3892/ijo.2012.1655
Pages: 2237-2244

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Abstract

MicroRNAs (miRNAs) are a large class of single-stranded RNA molecules involved in post-transcriptional gene silencing. miRNAs not only regulate various developmental and physiological processes but also are involved in cancer development. Additionally, they can be considered as biomarkers of some pathological processes. The aim of this study was to determine the expression levels of selected miRNA and zinc(II)-related genes (ZIP-1, BAX, MT2A and MT1A) in the non-tumor PNT1A prostate cell line in comparison with the prostate cancer cell lines 22Rv1, PC-3 and LNCaP after zinc(II) treatment. Using bioinformatic approaches we selected miRNAs with putative binding sites 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 23a in all tumor lines compared to non-tumor PNT1A (13.6-fold in 22Rv1, 7.3-fold in PC-3, 8.3-fold in LNCaP, p<0.01). We also observed that the 22Rv1 cell line has significantly higher expression of miRNA 224 in comparison to other cell lines. In addition, all tumor cell lines expressed significantly higher levels of miRNA 375 in 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 levels strongly suggest their potential to contribute to the diagnosis of prostate cancer and miRNA 224 eventually may be suitable for classification of primary tumors. The expression of miRNA 224 in 22Rv1 cell line was negatively correlated with increasing zinc(II) concentration only. Our experiments revealed significant negative correlation of miRNA 376 and MT2A in 22Rv1 and a negative correlation between miRNA 224 and MT1A in PC-3 cells which may denote possible direct regulation of MT genes by specific miRNAs in prostate cancer.

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