Abstract
PDGF (platelet derived growth factor) has been shown to play an important role in tumorigenesis, tumor growth, atherosclerosis and inflammation and other various pathologic settings. PDGF-B chain gene is 92% homologous to v-sis oncogene of the simian sarcoma virus. Thus PDGF-B gene is also called c-sis proto-oncogene. This report provides 3 TFOs (triplex-forming oligonucleotides) to inhibit the expression of c-sis/PDGF-B gene. The results from gel mobility shift analysis,in vitro transcription, DNase I footprinting and protein binding assays demonstrate that the TFOs we designed can form sequence-specific stable triplex with the target, and can effectively suppress the downstream gene transcription and inhibit transcription factors binding. They can be used for preparation of drugs to inhibit tumor growth and for the therapy of atherosclerosis, inflammation, etc.
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Abbreviations
- TFOs:
-
Triplex forming oligonucleotides
- SPE:
-
SIS proximal element
- PRR:
-
pyrimidine rich region
References
Doolittle, R. F., Hunkappiller, M. W., Hood, L. E. et al., Simian sarcoma virus oncogene, v-sis is derived from the gene (or genes) encoding platelet-derived growth factor, Science, 1983,221: 275.
Moser, H. E., Dervan, P. B. et al., Sequence-specific cleavage of double helical DNA by triple helix formation, Science, 1987,238: 645.
Jacob, J., Jagan, C. K., Dange, V. et al., Antiparallel polypurine phosphorothioate oligonucleotides form stable triplexes with the rat α1(I) collagen gene promoter and inhibit transcription in cultured rat fibroblasts, Nucleic Acids Res., 1997,25: 2182.
Darren, M. G., Keith, R. F., DNA triple helix formation at oligopurine sites containing multiple contiguous pyrimidines, Nucleic Acids Res., 1997,25: 3787.
Sharon, L. Y., Steven, H. K., Mark, D. M. et al., Triple helix formation inhibits transcription elongationin vitro, Proc. Natl. Acad. Sci. USA, 1991,88: 10023.
Charles, M., Scot, E., Jay, G. et al., Triplex formation by the human Ha-ras promoter inhibits Sp1 binding andin vitro transcription, J. Biol. Chem., 1994,269: 18232.
Liang, Y., Robinson, D. F., Dennig, J. et al., Transcriptional regulation of the SIS/PDGF-B gene in human osteosarcoma cells by the Sp family of transcription factors, J. Biol. Chem., 1996,271: 11792.
Jin, H. M., Robinson, D. F., Liang, Y. et al., SIS/PDGF-B promoter isolation and characterization of regulatory elements necessary for basal expression of the SIS/PDGF-B gene in U2-OS osteosarcoma cells, J. Biol. Chem., 1994,269: 28648.
Cooney, M., Czernuszewicz, G., Postel, E. H. et al., Site-specific oligonucleotide binding represses transcription of the human c-myc genein vitro, Science, 1988,241: 456.
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Liu, J., Xu, R., Jin, Y. et al. In vitro triplex formation and functional analysis of TFOs designed against human c-sis/PDGF-B proto-oncogene. Sci. China Ser. C.-Life Sci. 44, 83–91 (2001). https://doi.org/10.1007/BF02882076
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DOI: https://doi.org/10.1007/BF02882076