NDLI: Therapeutic potential of antisense oligodeoxynucleotides in downregulating p53 oncogenic mutations in cancers

Content Provider	Springer Nature Link
Author	Xie, Zhigang Chng, Wee Joo Tay, Kian Ghee Liu, Shaw Cheng Zhou, Jianbiao Chen, Chien Shing
Copyright Year	2010
Abstract	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.
Starting Page	221
Ending Page	228
Page Count	8
File Format	PDF
ISSN	01415492
Journal	Biotechnology Letters
Volume Number	33
Issue Number	2
e-ISSN	15736776
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-09-30
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	p53 Mutation Antisense oligodeoxynucleotide Carcinoma Biochemistry Applied Microbiology Biotechnology Microbiology
Content Type	Text
Resource Type	Article
Subject	Medicine Bioengineering Applied Microbiology and Biotechnology Biotechnology

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