Abstract
Ovarian cancer is the most lethal neoplasm of the female genital tract. Despite progress with chemotherapy, surgery and supportive care, the death rate remains extremely high. Gene silencing therapy represents a possible opportunity to advance the management of ovarian cancer patients. The concept of gene silencing therapy, which is based on RNA interference (RNAi) phenomenon, requires selection of targeted genes and development of a strategy for genetic drug development. Recently, plenty of research studies in ovarian cancer genetics have been published. Although they can be analyzed regarding candidate gene selection, the therapeutic effect of particular gene silencing can only be evaluated experimentally at this time. Obviously, the correct choice and application of a genetic drug delivery system determines the efficacy of gene silencing. Complexation of therapeutic nucleic acids with cationic polymers, cationic lipids, or their combination, represents a main strategy of non-virus-mediated delivery of genetic drug. Owing to a tendency of ovarian cancer to spread through the abdominal cavity, a delivery system should allow intraperitoneal mode of administration. Therefore, clinical application of RNAi may rely on a combination of biosciences and nanotechnology: in particular, identifying optimal small interfering RNAs (siRNAs) against optimal target genes and developing an efficient system for siRNA delivery into the cancer cells.
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References
Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498.
Omura, G.A. (2008) Progress in gynecologic cancer research: the gynecologic oncology group experience. Semin. Oncol. 35, 507–521.
Aigner, A. (2007) Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo. Appl. Microbiol. Biotechnol. 76, 9–21.
Paddison, P.J., Caudy, A.A., Sachidanandam, R. and Hannon, G.J. (2004) Short hairpin activated gene silencing in mammalian cells. Methods Mol. Biol. 265, 85–100.
Hannon, G.J. and Conklin, D.S. (2004) RNA interference by short hairpin RNAs expressed in vertebrate cells. Methods Mol. Biol. 257, 255–266.
Tchernitsa, O.I., Sers, C., Zuber, J., Hinzmann, B., Grips, M., Schramme, A., et al. (2004) Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells. Oncogene 23, 4536–4555.
Welsh, J.B., Zarrinkar, P.P., Sapinoso, L.M., Kern, S.G., Behling, C.A., Monk, B.J., et al. (2001) Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc. Natl. Acad. Sci. U.S.A. 98, 1176–1181.
Adib, T.R., Henderson, S., Perrett, C., Hewitt, D., Bourmpoulia, D., Ledermann, J., and Boshoff, C. (2004) Predicting biomarkers for ovarian cancer using gene-expression microarrays. Br. J. Cancer 90, 686–692.
Rogalla, P., Drechsler, K., Frey, G., Hennig, Y., Helmke, B., Bonk, U., and Bullerdiek, J. (1996) HMGI-C expression patterns in human tissues: Implications for the genesis of frequent mesenchymal tumors. Am. J. Pathol. 149, 775–779.
Gattas, G.J., Quade, B.J., Nowak, R.A., and Morton, C.C. (1999) HMGIC expression in human adult and fetal tissues and in uterine leiomyomata. Genes Chromosomes Cancer 25, 316–322.
Rogalla, P., Drechsler, K., Kazmierczak, B., Rippe, V., Bonk, U., and Bullerdiek, J. (1997) Expression of HMGI-C, a member of the high mobility group protein family, in a subset of breast cancers: relationship to histologic grade. Mol. Carcinog. 19, 153–156.
Meyer, B., Loeschke, S., Schultze, A., Weigel, T., Sandkamp, M., Goldmann, T., et al. (2007) HMGA2 overexpression in non-small cell lung cancer. Mol. Carcinog. 46, 503–511.
Abe, N., Watanabe, T., Suzuki, Y., Matsumoto, N., Masaki, T., Mori, T., et al. (2003) An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue. Br. J. Cancer 89, 2104–2109.
Chau, K.Y., Manfioletti, G., Cheung-Chau, K.W., Fusco, A., Dhomen, N., Sowden, J.C., et al. (2003) Derepression of HMGA2 gene expression in retinoblastoma is associated with cell proliferation. Mol. Med. 9, 154–165.
Miyazawa, J., Mitoro, A., Kawashiri, S., Chada, K.K., and Imai, K. (2004) Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Cancer Res. 64, 2024–2029.
Andrieux, J., Demory, J.L., Dupriez, B., Quief, S., Plantier, I., Roumier, C. et al. (2004) Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia. Genes Chromosomes Cancer 39, 82–87.
Berlingieri, M.T., Manfioletti, G., Santoro, M., Bandiera, A., Visconti, R., Giancotti, V., and Fusco, A. (1995) Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells. Mol. Cell Biol. 15, 1545–1553.
Pentimalli, F., Dentice, M., Fedele, M., Pierantoni, G.M., Cito, L., Pallante, P., et al. (2003) Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2. Cancer Res. 63, 7423–7427.
Malek, A., Bakhidze, E., Noske, A., Sers, C., Aigner, A., Schafer, R., and Tchernitsa, O. (2008) HMGA2 gene is a promising target for ovarian cancer silencing therapy. Int. J. Cancer 123, 348–356.
Elbashir, S.M., Martinez, J., Patkaniowska, A., Lendeckel, W., and Tuschl, T. (2001) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20, 6877–6888.
Yuan, B., Latek, R., Hossbach, M., Tuschl, T., and Lewitter, F. (2004) siRNA Selection Server: an automated siRNA oligonucleotide prediction server. Nucleic Acids Res. 32(Web Server issue), W130-W134.
Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., et al. (2004) Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res. 32, 936–948.
Amarzguioui, M. and Prydz, H. (2004) An algorithm for selection of functional siRNA sequences. Biochem. Biophys. Res. Commun. 316, 1050–1058.
Khvorova, A., Reynolds, A., and Jayasena, S.D. (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115, 209–216.
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Malek, A., Tchernitsa, O. (2010). Evaluation of Targets for Ovarian Cancer Gene Silencing Therapy: In Vitro and In Vivo Approaches. In: Min, WP., Ichim, T. (eds) RNA Interference. Methods in Molecular Biology, vol 623. Humana Press. https://doi.org/10.1007/978-1-60761-588-0_27
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DOI: https://doi.org/10.1007/978-1-60761-588-0_27
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