title: Selective inhibition of miR-21 by phage display screened peptide.
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.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India.
authors.forename: Debojit
authors.initials: D
authors.lastname: Bose
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India.
authors.forename: Smita
authors.initials: S
authors.lastname: Nahar
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Rai
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India.
authors.forename: Arjun
authors.initials: A
authors.lastname: Ray
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India.
authors.forename: Kausik
authors.initials: K
authors.lastname: Chakraborty
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India National Chemical Laboratory, CSIR, Dr. Homi Bhabha Road, Pune 411008, India souvik@igib.res.in.
authors.forename: Souvik
authors.initials: S
authors.lastname: Maiti
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D061505:Cell Surface Display Techniques; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology; D009711:Nucleotides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012322:RNA Precursors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009711:Nucleotides; D010455:Peptides; D012322:RNA Precursors
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