<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Nahar, Smita</style></author><author><style face="normal" font="default" size="100%">Singh, Amrita</style></author><author><style face="normal" font="default" size="100%">Morihiro, Kunihiko</style></author><author><style face="normal" font="default" size="100%">Moai, Yoshihiro</style></author><author><style face="normal" font="default" size="100%">Kodama, Tetsuya</style></author><author><style face="normal" font="default" size="100%">Obika, Satoshi</style></author><author><style face="normal" font="default" size="100%">Maiti, Souvik</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Systematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-21</style></title><secondary-title><style face="normal" font="default" size="100%">Biochemistry</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">55</style></volume><pages><style face="normal" font="default" size="100%">7023-7032</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">miRNAs 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 &lt;= 1.05 x 10(8) M-1. We also observed enhanced serum stability for SeLNA RNA duplexes with a half-life of &lt;= 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.</style></abstract><issue><style face="normal" font="default" size="100%">50</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">2.876</style></custom4></record></records></xml>