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http://dx.doi.org/10.7314/APJCP.2013.14.2.765

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.2, 2013 , pp. 765-768 More about this Journal
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
Prostate cancer; miRNAs; metformin; miRNA profiling;
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1 Baranwal S, Alahari SK (2010) miRNA control of tumor cell invasion and metastasis. Int J Cancer, 126, 1283-90.
2 Benjamini, Y, Hochberg Y (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B, 57, 289-300.
3 Ben SI, Laurent K, Loubat A, et al (2008). The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene, 27, 3576-86.   DOI   ScienceOn
4 Decensi A, Puntoni M, Goodwin P, et al (2010). Metformin and cancer risk in diabetic patients, a systematic review and meta-analysis. Cancer Prev Res, 3, 1451-61.   DOI   ScienceOn
5 De Hoon MJL, Imoto S, Nolan JN, Miyano S (2004). Open source clustering software. Bioinformatics, 20, 1453-4.   DOI   ScienceOn
6 Gotlieb WH, Saumet J, Beauchamp MC, et al (2008). In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. Gynecol Oncol, 110, 246-50.   DOI   ScienceOn
7 Hernes E, Kyrdalen A, Kvale R, et al (2010). Initial management of prostate cancer, first year experience with the Norwegian National Prostate Cancer Registry. BJU Int, 105, 805-11.   DOI   ScienceOn
8 Iorio MV, Croce CM (2009). MicroRNAs in cancer, small molecules with a huge impact. J Clin Oncol, 27, 5848-56.   DOI   ScienceOn
9 Isakovic A, Harhaji L, Stevanovic D, et al (2007). Dual antiglioma action of metformin, cell cycle arrest and mitochondria-dependent apoptosis. Cell Mol Life Sci, 64, 1290-302.   DOI
10 Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics, 2009. CA Cancer J Clin, 59, 225-49.   DOI   ScienceOn
11 Kong DJ, Li YW, Wang ZW, Banerjee S, et al (2009). miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells, 27, 1712-21.   DOI   ScienceOn
12 Landman GW, Kleefstra N, van Hateren KJ, et al (2010). Metformin associated with lower cancer mortality in type 2 diabetes, ZODIAC-16. Diabetes Care, 33, 322-6.   DOI   ScienceOn
13 Libby G, Donnelly LA, Donnan PT, et al (2009). New users of metformin are at low risk of incident cancer, a cohort study among people with type 2 diabetes. Diabetes Care, 32, 1620-5.   DOI   ScienceOn
14 Lin SL, Chiang A, Chang D, Ying SY (2008). Loss of mir-146a function in hormone-refractory prostate cancer. RNA, 14, 417-24.   DOI   ScienceOn
15 Mattie MD, Benz CC, Bowers J, et al (2006). Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer, 5, 24   DOI   ScienceOn
16 Murtola TJ, Tammela TL, Lahtela J, et al (2008). Antidiabetic medication and prostate cancer risk, a population-based case-control study. Am J Epidemiol, 168, 925-31   DOI   ScienceOn
17 Porkka KP, Pfeiffer MJ, Waltering KK et al (2007). MicroRNA expression profiling in prostate cancer. Cancer Res, 67, 6130-5.   DOI   ScienceOn
18 Schaefer A, Jung M, Kristiansen G, et al (2009). MicroRNAs and cancer, current state and future perspectives in urologic oncology. Urol Oncol, 28, 4-13.
19 Sharov AA, Dudekula DB, Ko MSH (2005). Principal component and significance analysis of microarrays with NIA Array Analysis tool. Bioinformatics, 21, 2548-9.   DOI   ScienceOn
20 Shi XB, Xue LR, Yang J, et al (2007). An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA, 104, 19983-88.   DOI   ScienceOn
21 Vrba L, Jensen TJ, Garbe JC, et al (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One, 5, 8697.   DOI   ScienceOn
22 Wright JL, Stanford JL (2009). Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control, 20,1617-22.   DOI   ScienceOn