@article {43406,
	title = {Systematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-21},
	journal = {Biochemistry},
	volume = {55},
	year = {2016},
	month = {DEC},
	pages = {7023-7032},
	abstract = {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 <= 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.},
	doi = {10.1021/acs.biochem.6b00895},
	author = {Nahar, Smita and Singh, Amrita and Morihiro, Kunihiko and Moai, Yoshihiro and Kodama, Tetsuya and Obika, Satoshi and Maiti, Souvik}
}
