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|Title:||Therapeutic potential of antisense oligodeoxynucleotides in downregulating p53 oncogenic mutations in cancers|
|Authors:||Xie, Z. |
|Citation:||Xie, Z., Chng, W.J., Tay, K.G., Liu, S.C., Zhou, J., Chen, C.-S. (2011-02). Therapeutic potential of antisense oligodeoxynucleotides in downregulating p53 oncogenic mutations in cancers. Biotechnology Letters 33 (2) : 221-228. ScholarBank@NUS Repository. https://doi.org/10.1007/s10529-010-0423-5|
|Abstract:||Purpose of work: Mutation of the p53 gene is the most common genetic alteration in human cancers. Our study proposes to rationally design a p53 antisense oligonucleotide (ASO) repository, which contains a series of ASOs containing single nucleotide differences to discriminate between each mutant and wild type (WT) p53. The Sfold software was used to predict target-accessibility and we designed an initial series of antisense oligonucleotides (ASO) that target the p53 mutants A161T, R175H and R249S. Western-blot analysis indicated that ASOs strongly inhibited the expression of p53 mutants in a panel of human tumor cell lines (SNU-449, SK-BR-3 and PLC/PRF/5) while having little effect on the expression of WT p53 (HepG2 cells). In three cancer lines harboring each of the p53 mutations, mutant-specific ASO treatment led to a dose-dependent inhibition of cell growth, cell viability, colony formation and invasion, and expression of mutant p53-dependent survival proteins. Our preliminary results indicate that a single nucleotide difference in ASOs can discriminate between mutant and WT p53. These observations support the hypothesis that a p53 ASO repository can be a potentially valuable tool to knock down oncogenic mutant p53 and warrant the testing of a p53 ASO repository in in vivo settings. © 2010 Springer Science+Business Media B.V.|
|Source Title:||Biotechnology Letters|
|Appears in Collections:||Staff Publications|
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