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Therapeutic Potential of an Anti-diabetic Drug, Metformin: Alteration of miRNA expression in Prostate Cancer Cells

  • Avci, Cigir Biray (Department of Medical Biology, Ege University Medical School) ;
  • Harman, Ece (Department of Endocrinology, Izmir Katip Celebi University, Ataturk Training and Research Hospital) ;
  • Dodurga, Yavuz (Department of Medical Biology, Pamukkale University Medical Faculty) ;
  • Susluer, Sunde Yilmaz (Department of Medical Biology, Ege University Medical School) ;
  • Gunduz, Cumhur (Department of Medical Biology, Ege University Medical School)
  • Published : 2013.02.28

Abstract

Background and Aims: Prostate cancer is the most commonly diagnosed cancer in males in many populations. Metformin is the most widely used anti-diabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anti-cancer drug. Metformin inhibits the proliferation of a range of cancer cells including prostate, colon, breast, ovarian, and glioma lines. MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that downregulate gene expression. We aimed to evaluate the effects of metformin treatment on changes in miRNA expression in PC-3 cells, and possible associations with biological behaviour. Materials and Methods: Average cell viability and cytotoxic effects of metformin were investigated at 24 hour intervals for three days using the xCELLigence system. The $IC_{50}$ dose of metformin in the PC-3 cells was found to be 5 mM. RNA samples were used for analysis using custom multi-species microarrays containing 1209 probes covering 1221 human mature microRNAs present in miRBase 16.0 database. Results: Among the human miRNAs investigated by the arrays, 10 miRNAs were up-regulated and 12 miRNAs were down-regulated in the metformin-treated group as compared to the control group. In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important. This study may emphasize a new role of metformin on the regulation of miRNAs in prostate cancer.

Keywords

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