Abstract
The PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14) is upregulated in approximately 60% of breast cancers, some of which exhibit gene amplification. In contrast, PRDM14 is not expressed in normal, and differentiated tissues. PRDM14+ breast cancer cells are resistant to chemotherapy drugs, are tumorigenic, and metastasize to the lungs. It is commonly assumed that genes that are overexpressed in cancers, such as PRDM14, are effective targets for new therapies that specifically abrogate the expression of these genes. RNA interference of PRDM14, a gene expressed by breast cancer cells, reduced the size of tumors and lung metastases in nude mice. In this chapter, we introduce the concept and methods to develop and apply systematically injected small interfering RNA therapy for breast cancer models in vivo.
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References
Mzoughi S, Tan YX, Low D et al (2016) The role of PRDMs in cancer: one family, two sides. Curr Opin Genet Dev 36:83–91
Yamaji M, Seki Y, Kurimoto K et al (2008) Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 40:1016–1022
Yamaji M, Ueda J, Hayashi K et al (2013) PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell Stem Cell 12:368–382
Nishikawa N, Toyota M, Suzuki H et al (2007) Gene amplification and overexpression of PRDM14 in breast cancers. Cancer Res 67:9649–9657
Dettman EJ, Justice MJ (2008) The zinc finger SET domain gene Prdm14 is overexpressed in lymphoblastic lymphomas with retroviral insertions at Evi32. PLoS One 3:e3823
Taniguchi H, Hoshino D, Moriya C et al (2017) Silencing PRDM14 expression by an innovative RNAi therapy inhibits stemness, tumorigenicity, and metastasis of breast cancer. Oncotarget 8:46856–46874
Moriya C, Taniguchi H, Miyata K et al (2017) Inhibition of PRDM14 expression in pancreatic cancer suppresses cancer stem-like properties and liver metastasis in mice. Carcinogenesis 38:638–648
Ui-Tei K, Naito Y, Saigo K (2006) Essential notes regarding the design of functional siRNAs for efficient mammalian RNAi. J Biomed Biotechnol 2006:1–8
Naito Y, Yoshimura J, Morishita S et al (2009) siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect. BMC Bioinformatics 10:392
Ui-Tei K, Naito Y, Zenno S et al (2008) Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucleic Acids Res 36:2136–2151
Pittella F, Cabral H, Maeda Y et al (2014) Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles. J Control Release 178:18–24
Shimizu H, Hori Y, Kaname S et al (2010) siRNA-based therapy ameliorates glomerulonephritis. J Am Soc Nephrol 21:622–633
Acknowledgments
This work was supported by the Department of Research Promotion, Practical Research for Innovative Cancer Control, Ministry of Health, Labour and Welfare, and the Japan Agency for Medical Research and Development (AMED). We wish to thank Prof. Kazunori Kataoka from the Innovation Center of NanoMedicine for the DDSs and Prof. Yukikazu Natori and Associate professor Kumiko Ui-Tei from the University of Tokyo for chimera siRNA and selection of highly effective siRNA sequences for RNAi. We also would like to thank Editage (www.editage.jp) for English language editing.
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Taniguchi, H., Imai, K. (2019). Silencing PRDM14 via Oligonucleotide Therapeutics Suppresses Tumorigenicity and Metastasis of Breast Cancer. In: Dinesh Kumar, L. (eds) RNA Interference and Cancer Therapy. Methods in Molecular Biology, vol 1974. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9220-1_18
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DOI: https://doi.org/10.1007/978-1-4939-9220-1_18
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Publisher Name: Humana, New York, NY
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Online ISBN: 978-1-4939-9220-1
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