Use of RNA aptamers for the modulation of cancer cell signaling.
Aptamers are in vitro evolved molecules that bind to target proteins with high affinity and specificity by adapting three-dimensional structures upon binding. Because cancer cells exhibit the activation of signaling pathways that are not usually activated in normal cells, RNA aptamers against such a cancer cell-specific signal can be useful lead molecules for cancer gene therapy. The Wnt/beta-catenin signaling pathway plays important roles in a critical initiating event in the formation of various human cancers. Because mutations in beta-catenin have been found to be responsible for human tumorigenesis, beta-catenin is the molecular target for effective anticancer therapies. Here, we describe the selection of RNA aptamers against beta-catenin/T-Cell Factor (TCF) proteins and their intracellular expression as intramers. The RNA aptamers acted as central inhibitory players for multiple oncogenic functions of beta-catenin in colon cancer cells. These data provide the proof-of-principle for the use of RNA aptamers for an effective anticancer gene therapy.
Jeong
Sunjoo
S
National Research Laboratory for RNA Cell Biology, Department of Molecular Biology, Dankook University, Gyeonggi-do, Republic of Korea.
Lee
Hee Kyu
HK
Kim
Mee Young
MY
D000818:Animals; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D052156:SELEX Aptamer Technique; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D052157:Aptamers, Nucleotide; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D005982:Glutathione Transferase