Selective inhibition of miR-21 by phage display screened peptide |
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Authors: | Debojit Bose Smita Nahar Manish Kumar Rai Arjun Ray Kausik Chakraborty Souvik Maiti |
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Institution: | 1.Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India;2.Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India;3.National Chemical Laboratory, CSIR, Dr. Homi Bhabha Road, Pune 411008, India |
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Abstract: | miRNAs are nodal regulators of gene expression and deregulation of miRNAs is causally associated with different diseases, including cancer. Modulation of miRNA expression is thus of therapeutic importance. Small molecules are currently being explored for their potential to downregulate miRNAs. Peptides have shown to have better potency and selectivity toward their targets but their potential in targeting and modulating miRNAs remain unexplored. Herein, using phage display we found a very selective peptide against pre-miR-21. Interestingly, the peptide has the potential to downregulate miR-21, by binding to pre-miR-21 and hindering Dicer processing. It is selective towards miR-21 inside the cell. By antagonising miR-21 function, the peptide is able to increase the expression of its target proteins and thereby increase apoptosis and suppress cell proliferation, invasion and migration. This peptide can further be explored for its anti-cancer activity in vivo and may be even extended to clinical studies. |
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