title: Screening of Pre-miRNA-155 Binding Peptides for Apoptosis Inducing Activity Using Peptide Microarrays.
abstract: MicroRNA-155, one of the most potent miRNAs that suppress apoptosis in human cancer, is overexpressed in numerous cancers, and it displays oncogenic activity. Peptide microarrays, constructed by immobilizing 185 peptides containing the C-terminal hydrazide onto epoxide-derivatized glass slides, were employed to evaluate peptide binding properties of pre-miRNA-155 and to identify its binding peptides. Two peptides, which were identified based on the results of peptide microarray and in vitro Dicer inhibition studies, were found to inhibit generation of mature miRNA-155 catalyzed by Dicer and to enhance expression of miRNA-155 target genes in cells. In addition, the results of cell experiments indicate that peptide inhibitors promote apoptotic cell death via a caspase-dependent pathway. Finally, observations made in NMR and molecular modeling studies suggest that a peptide inhibitor preferentially binds to the upper bulge and apical stem-loop region of pre-miRNA-155, thereby suppressing Dicer-mediated miRNA-155 processing.
authors.affiliation: National Creative Research Center for Biofunctional Molecules, Department of Chemistry, Yonsei University , Seoul 03722, Korea.
authors.forename: Jaeyoung
authors.initials: J
authors.lastname: Pai
authors.affiliation: Department of Chemistry and Education, Seoul National University , Seoul 08826, Korea.
authors.forename: Soonsil
authors.initials: S
authors.lastname: Hyun
authors.affiliation: National Creative Research Center for Biofunctional Molecules, Department of Chemistry, Yonsei University , Seoul 03722, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Hyun
authors.affiliation: National Creative Research Center for Biofunctional Molecules, Department of Chemistry, Yonsei University , Seoul 03722, Korea.
authors.forename: Seong-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Advanced Analysis Center, Korea Institute of Science and Technology , Seoul 02792, Korea.
authors.forename: Won-Je
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: CKD Research Institute , 315-20, Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17006, Korea.
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Advanced Analysis Center, Korea Institute of Science and Technology , Seoul 02792, Korea.
authors.forename: Nak-Kyoon
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Education, Seoul National University , Seoul 08826, Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
authors.affiliation: National Creative Research Center for Biofunctional Molecules, Department of Chemistry, Yonsei University , Seoul 03722, Korea.
authors.forename: Injae
authors.initials: I
authors.lastname: Shin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D040081:Protein Array Analysis
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D010455:Peptides