Screening of Pre-miRNA-155 Binding Peptides for Apoptosis Inducing Activity Using Peptide Microarrays

Title
Screening of Pre-miRNA-155 Binding Peptides for Apoptosis Inducing Activity Using Peptide Microarrays
Authors
Jaeyoung PaiSoonsil HyunJi Young HyunSeong-Hyun Park김원제Sung-Hun Bae김낙균Jaehoon YuInjae Shin
Keywords
HSP70; Apoptozole; Pre-miRNA-155; Peptide microarray; NMR; Apoptosis; miRNA; RNA; structure; model
Issue Date
2016-01
Publisher
Journal of the American Chemical Society
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.
URI
http://pubs.kist.re.kr/handle/201004/58460
ISSN
00027863
Appears in Collections:
KIST Publication > Article
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