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

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 potentialefficacy of this agent as an anti-cancer drug. Metformin inhibits the proliferation of a range of cancer cellsincluding prostate, colon, breast, ovarian, and glioma lines. MicroRNAs (miRNAs) are a class of small, noncoding,single-stranded RNAs that downregulate gene expression. We aimed to evaluate the effects of metformintreatment 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 hourintervals for three days using the xCELLigence system. The IC50 dose of metformin in the PC-3 cells was foundto be 5 mM. RNA samples were used for analysis using custom multi-species microarrays containing 1209probes covering 1221 human mature microRNAs present in miRBase 16.0 database.
Results: Among the humanmiRNAs investigated by the arrays, 10 miRNAs were up-regulated and 12 miRNAs were down-regulated in themetformin-treated group as compared to the control group. In conclusion, expression changes in miRNAs ofmiR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important. Thisstudy may emphasize a new role of metformin on the regulation of miRNAs in prostate cancer.