01733nas a2200205   4500008004100000022001400041245006900055210006800124260007200192300001400264490000700278520102700285100001801312700001701330700002301347700001501370700002401385700001801409856010001427       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  uhttps://library.ncl.res.in/content/selective-inhibition-mir-21-phage-display-screened-peptide-002061nas a2200193   4500008004100000022001400041245008600055210006900141260000800210300001200218490000700230520140400237100001801641700002701659700001501686700002801701700001701729856012101746       2022                        eng d  a2162-253100aSmall molecule quercetin binds MALAT1 triplex and modulates its cellular function0 aSmall molecule quercetin binds MALAT1 triplex and modulates its   cDEC  a241-2560 v303 a<p>
	The triple-helix structure at the 30 end of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non -cod-ing RNA, has been considered to be a target for modulating the oncogenic functions of MALAT1. This study examines the binding of quercetin-a known triplex binding molecule-to the MALAT1 triplex. By employing UV-visible spectroscopy, circular dichroism spectroscopy, and isothermal titration calo-rimetry, we observed that quercetin binds to the MALAT1 triplex with a stoichiometry of 1:1 and Kd of 495 +/- 61 nM, along with a negative change in free energy, indicating a spontaneous interaction. Employing real-time PCR measurements, we observed around 50% downregulation of MALAT1 transcript levels in MCF7 cells, and fluorescence in situ hybridization (FISH) experiments showed concomitantly reduced levels of MALAT1 in nuclear speckles. This interaction is likely a result of a direct interaction between the molecule and the RNA, as indicated by a transcription-stop experiment. Further, tran-scriptome-wide analysis of alternative splicing changes induced by quercetin revealed modulation of MALAT1 downstream genes. Collectively, our study shows that quercetin strongly binds to the MALAT1 triplex and modulates its functions. It can thus be used as a scaffold for further development of ther-apeutics or as a chemical tool to understand MALAT1 func-tions.</p>
1 aRakheja, Isha1 aAnsari, Asgar, Hussain1 aRay, Arjun1 aJoshi, Dheeraj, Chandra1 aMaiti, Souvi  uhttps://library.ncl.res.in/content/small-molecule-quercetin-binds-malat1-triplex-and-modulates-its-cellular-function