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.
Bibliographical noteFunding Information:
This study was supported financially by the National Creative Research Initiative (2010-0018272 to I.S.) and NRL (2011- 0028483 to J.Y) programs, KIST (2 V04081 and 2E25570 to N.-K.K) and NRF (2015R1A2A2A04005596 to N.-K.K) in Korea.
© 2016 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Colloid and Surface Chemistry