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Designing siRNA for Silencing Polo-Like Kinase 1 (Plk1) Gene of Prostate Cancer


:10.22362/ijcert/2017/v4/i2/xxxx [UNDER PROCESS]

Prostate cancer is the most commonly occurring cancer in American men, next to skin cancer. Existing treatment options and surgical intervention are unable to manage this cancer effectively. Therefore, continuing efforts are ongoing to establish a novel mechanism based targets and strategies for its management. PLK1 plays a key role in the mitotic entry of proliferating cells and regulates many aspects of mitosis which are necessary for successful cytokinesis. PLK1 is overexpressed in many tumour types with aberrant elevation frequently constituting a prognostic indicator of poor disease outcome and our study indicate that PLK1 could be an excellent target for the treatment as well as chemoprevention of prostate cancer.

Jayaprakash. P, “Designing siRNA for Silencing Polo-Like Kinase 1 (Plk1) Gene of Prostate Cancer”, International Journal Of Computer Engineering In Research Trends, 4(2):25-32, February-2017.

Keywords : Prostate cancer, PLK1 gene and siRNA

1)	Landis, SH., Murray, T., Bolden, S. and Wing, P.A., (1998). Cancer statistics, 1998. CA. Cancer J. Clin. 48: 6-29.
2)	Jemal, A., Tiwari, R.C., Murray, T., Ghafoor, A., Samuels, A., Ward, E., Feuer, E. J. and Thun, M. J. (2004). Cancer statistics. CA. Cancer J. Clin. 54: 8-29.
3)	Reagan-Shaw, S. and Ahmad, N., (2005). Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer. FASEB. J. 19: 611-613.
4)	Talcott, J.A., Rieker, P., Clark, J.A., Propert, K.J., Weeks, J.C., Beard, C.J., Wishnow, K.I., Kaplan, I., Loughlin, K.R., Richie, J.P. and Kantoff, P.W. (1998). Patient-reported symptoms after primary therapy for early prostate cancer: Results of a prospective cohort study. J. Clin. Oncol. 16: 275-283.
5)	Quinn, M. and Babb, P. (2002). Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: International comparisons. BJU. Int. 90: 162-164.
6)	Herbert, J.R., Ghumare, S.S. and Gupta, P.C. (2006). Stage at diagnosis and relative differences in breast and prostrate cancer incidence in India: Comparison with the United States. Asian. Pac. J. Cancer. Prev. 7: 547-555.
7)	Daskivich, T.J. and Oh, W.K. (2006). Failure of gonadotropin-releasing hormone agonists with and without sterile abscess formation at depot sites: insight into mechanisms? Urology 67: 15-17.
8)	Gallagher, E. and Gapstur, R. (2006). Hormone-refractory prostrate cancer : A shifting paradigm in treatment. Clin. J. Oncol. Nurs. 10: 233-240.
9)	Golsteyn, R.M., Schultz, S.J., Bartek, J., Ziemiecki, A., Ried, T. and Nigg, E.A. (1994). Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5. J. Cell Sci. 107: 1509-1517.
10)	Glover, D.M., Hagan, I.M. and Tavares, A.A. (1998). Polo-like kinases: A team that plays throughout mitosis. Genes Dev. 12: 3777-3787.
11)	Donaldson, M.M., Tavares, A.A., Ohkura, H., Deak, P. and Glover, D.M., (2001b). Metaphase arrest with centromere separation in polo mutants of Drosophila. J. Cell Biol. 153: 663-676.
12)	Lane, H.A. and Nigg, E.A. (1996). Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J. Cell Biol. 135(6 Pt 2): 1701-1713.
13)	Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M. A. and Nasmyth, K. (2001). Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell. 105:  459-472.
14)	Sumara, I., Vorlaufer, E., Stukenberg, P.T., Kelm, O., Redemann, N., Nigg, E.A. and Peters, J.M. (2002). The dissociation of cohesin from chromosomes in prophase is regulated by polo-like kinase. Mol. Cell 9: 515-525.
15)	Lansing,T.J., McConnell, R.T., Duckett, D.R., Spehar, G.M., Knick, V.B., Hassler, D.F., Noro, N., Furuta, M., Emmitte, K.A. and Gilmer, T.M. (2007). In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol. Cancer Ther.  6: 450-459.
16)	van Vugt, M.A., Bras, A. and Medema, R.H. (2004a). Polo-like kinase-1 controls recovery from a G2 DNA damage-induced arrest in mammalian cells. Mol. Cell. 15: 799-811.
17)	van Vugt, M.A., van de Weerdt, B.C., Vader, G., Janssen, H., Calafat, J., Klompmaker, R., Wolthuis, R.M. and Medema, R.H. (2004b). Polo-like kinase-1 is required for bipolar spindle formation but is dispensable for anaphase promoting complex/Cdc20 activation and initiation of cytokinesis. J. Biol. Chem. 279: 36841-36854.
18)	McInnes, C., Mezna, M. and Fischer, P.M. (2005). Progress in the discoveryof polo-like kinase inhibitors. Curr. Top. Med. Chem. 5: 181-197. 
19)	McInnes, C., Mazumdar, A., Mezna, M., Meades, C., Midgley, C., Scaerou, F., Carpenter, L., Mackenzie, M., Taylor, P. and Walkinshaw, M. (2006). Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance. Nat. Chem. Biol. 2(11): 608-617.
20)	Seong, Y.S., Kamijo, K., Lee, J.S., Fernandez, E., Kuriyama, R., Miki, T. and Lee, K.S. (2002). A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells. J. Biol. Chem. 277(35): 32282-32293.
21)	Leung, G.C., Hudson, J.W., Kozarova, A., Davidson, A., Dennis, J.W. and Sicheri, F. (2002). The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization. Nat. Struct. Biol. 9: 719-724.
22)	Golsteyn, R.M., Mundt, K.E., Fry, A.M. and Nigg, E.A. (1995). Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. J. Cell Biol. 129(6): 1617-1628.
23)	Hamanaka, R., Smith, M.R., O'Connor, P.M., Maloid, S., Mihalic, K., Spivak, J.L., Longo, D.L. and Ferris, D.K. (1995). Polo-like kinase is a cell cycle-regulated kinase activated during mitosis. J. Biol. Chem. 270(36): 21086-21091.
24)	Hamanaka, R., Maloid, S., Smith, M.R., O'Connell, C.D., Longo, D.L. Ferris, D.K. (1994). Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase. Cell. Growth. Differ. 5(3): 249-257.
25)	Holtrich, U., Wolf, G., Brauninger, A., Karn, T., Bohme, B., Rubsamen-Waigmann, H. and Strebhardt, K. (1994). Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. Proc. Natl. Acad. Sci. USA. 91: 1736- 1740.
26)	Smith, M.R., Wilson, M.L. and Hamanaka, R. (1997). Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase. Biochem. Biophys. Res. Commun. 234: 397-405.
27)	Zhang, C., Pei, J., Kumar, D., Sakabe, I., Boudreau, H.E., Gokhale, P.C. and Kasid, U.N. (2007). Antisense oligonucleotides: target validation and development of systemically delivered therapeutic nanoparticles. Methods. Mol. Biol. 361:163-185.
28)	Spänkuch, B., Steinhauser, I., Wartlick, H., Kurunci-Csacsko, E., Strebhardt, K.I., Langer, K. (2008). Downregulation of Plk1 expression by receptor mediated uptake of antisense oligonucleotide-loaded nanoparticles. Neoplasia 10(3): 223-234.
29)	Sui, G., Soohoo, C., Affar, B., Gay, F., Shi, Y. and Forrester, W.C. (2002). A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci. USA. 99: 5515-5520. 

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