<?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%">Totary-Jain, H.</style></author><author><style face="normal" font="default" size="100%">Sanoudou, D.</style></author><author><style face="normal" font="default" size="100%">Ben-Dov, I. Z.</style></author><author><style face="normal" font="default" size="100%">Dautriche, C. N.</style></author><author><style face="normal" font="default" size="100%">Guarnieri, P.</style></author><author><style face="normal" font="default" size="100%">Marx, S. O.</style></author><author><style face="normal" font="default" size="100%">Tuschl, T.</style></author><author><style face="normal" font="default" size="100%">Marks, A. R.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Reprogramming of the microRNA transcriptome mediates resistance to rapamycin</style></title><secondary-title><style face="normal" font="default" size="100%">J Biol ChemJ Biol ChemJ Biol Chem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">The Journal of biological chemistry</style></alt-title><short-title><style face="normal" font="default" size="100%">The Journal of biological chemistryThe Journal of biological chemistry</style></short-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antibiotics, Antineoplastic/*pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Neoplasm/*drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Neoplastic/*drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">MicroRNAs/*biosynthesis</style></keyword><keyword><style  face="normal" font="default" size="100%">Neoplasm Proteins/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Neoplasm/*biosynthesis</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction/drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">Sirolimus/*pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Time Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">TOR Serine-Threonine Kinases/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome/*drug effects</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Mar 1</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">9</style></number><volume><style face="normal" font="default" size="100%">288</style></volume><pages><style face="normal" font="default" size="100%">6034-44</style></pages><isbn><style face="normal" font="default" size="100%">1083-351X (Electronic)0021-9258 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation that is often deregulated in cancer. Inhibitors of mTOR, including rapamycin and its analogues, are being evaluated as antitumor agents. For their promise to be fulfilled, it is of paramount importance to identify the mechanisms of resistance and develop novel therapies to overcome it. Given the emerging role of microRNAs (miRNAs) in tumorigenesis, we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Long-term rapamycin treatment showed extensive reprogramming of miRNA expression, characterized by up-regulation of miR-17-92 and related clusters and down-regulation of tumor suppressor miRNAs. Inhibition of members of the miR-17-92 clusters or delivery of tumor suppressor miRNAs restored sensitivity to rapamycin. This study identifies miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors. It also identifies potential markers to assess the efficacy of treatment and provides novel therapeutic targets to treat rapamycin-resistant tumors.</style></abstract><accession-num><style face="normal" font="default" size="100%">23300087</style></accession-num><notes><style face="normal" font="default" size="100%">Totary-Jain, HanaSanoudou, DespinaBen-Dov, Iddo ZDautriche, Cula NGuarnieri, PaoloMarx, Steven OTuschl, ThomasMarks, Andrew RengK99 HL109133/HL/NHLBI NIH HHS/K99HL109133/HL/NHLBI NIH HHS/F32HL088815/HL/NHLBI NIH HHS/Howard Hughes Medical Institute/F32 HL088815/HL/NHLBI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't2013/01/10 06:00J Biol Chem. 2013 Mar 1;288(9):6034-44. doi: 10.1074/jbc.M112.416446. Epub 2013 Jan 8.</style></notes><custom2><style face="normal" font="default" size="100%">3585042</style></custom2><auth-address><style face="normal" font="default" size="100%">Department of Physiology and Cellular Biophysics, the Clyde and Helen Wu Center for Molecular Cardiology, Columbia University, New York, New York 10032, USA. ht2167@columbia.edu</style></auth-address></record></records></xml>