title: The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation.
abstract: p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short single-stranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Farooq
authors.initials: F
authors.lastname: Rashid
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Shah
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Hassaan M
authors.initials: HM
authors.lastname: Awan
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Luo
authors.affiliation: School of Life Sciences and Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, Anhui Province 230027, China shange@ustc.edu.cn.
authors.forename: Ge
authors.initials: G
authors.lastname: Shan
mesh_terms: D061605:Administration, Intravenous; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000235:genetics*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000302:isolation & purification*; D001483:Base Sequence; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000473:pathology; D052156:SELEX Aptamer Technique; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000596:Amino Acids; D052157:Aptamers, Nucleotide; D050505:Mutant Proteins; D016159:Tumor Suppressor Protein p53
keywords: RNA aptamer; SELEX; contrast screening; p53; tumor