01732nas a2200205   4500008004100000022001400041245006900055210006800124260007200192300001400264490000700278520102700285100001801312700001701330700002301347700001501370700002401385700001801409856009901427       2015                        eng d  a0305-104800aSelective inhibition of miR-21 by phage display screened peptide0 aSelective inhibition of miR21 by phage display screened peptide  aGREAT CLARENDON ST, OXFORD OX2 6DP, ENGLANDbOXFORD UNIV PRESScAPR  a4342-43520 v433 a<p>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.</p>1 aBose, Debojit1 aNahar, Smita1 aRai, Manish, Kumar1 aRay, Arjun1 aChakraborty, Kausik1 aMaiti, Souvik  uhttp://library.ncl.res.in/content/selective-inhibition-mir-21-phage-display-screened-peptide-002387nas a2200205   4500008004100000245014100041210006900182260000800251300001400259490000700273520164000280100001701920700001801937700002301955700002001978700002001998700001902018700001802037856012602055       2016                        eng d00aSystematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-210 aSystematic evaluation of biophysical and functional characterist  cDEC  a7023-70320 v553 amiRNAs constitute an important layer of gene regulation mediated by sequence-specific targeting of mRNAs. Aberrant expression of miRNAs contributes to a host of pathological states. Promoting cancer, miR-21 is upregulated in variety of cancers and promotes tumor progresion by suppressing a network of tumor suppressor genes. Here we describe a novel class of bicyclic RNA analogues, selenomethylene-locked nucleic acid (SeLNA), that display high affinity, improved metabolic stability, and increased potency for miR-21 inhibition. The thermal stability (T-m) for duplexes was increased significantly with incorporation of SeLNA monomers as compared to that of the unmodified DNA RNA hybrid. A comprehensive thermodynamic profile obtained by isothermal titration calorimetry revealed a favorable increase in the enthalpy of hybridization for SeLNA containing DNA and target RNA heteroduplexes. SeLNA modifications displayed remarkable binding affinity for miR-21 target RNA with a K-a of <= 1.05 x 10(8) M-1. We also observed enhanced serum stability for SeLNA RNA duplexes with a half-life of <= 36 h. These in vitro results were well correlated with the antisense activity in cancer cells imparting up to similar to 91% inhibition of miR-21. The functional impact of SeLNA modifications on miR-21 inhibition was further gauged by investigating the migration and invasion characterisitics of cancer cells, which were drastically reduced to similar to 49 and similar to 55%, respectively, with SeLNA having four such modifications. Our findings demonstrate SeLNA as a promising candidate for therapeutics for disease associated miRNAs.1 aNahar, Smita1 aSingh, Amrita1 aMorihiro, Kunihiko1 aMoai, Yoshihiro1 aKodama, Tetsuya1 aObika, Satoshi1 aMaiti, Souvik  uhttp://library.ncl.res.in/content/systematic-evaluation-biophysical-and-functional-characteristics-selenomethylene-locked