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Chen, Ting-Wen; Singh, Vivek P.; Caesar-Johnson, Samantha J.; Hutter, Carolyn M.; Sun, Qiang; Wu, Ye; Gehlenborg, Nils; Zhang, Hailei; Broom, Bradley M.; Ling, Shiyun; Rao, Arvind; Kundra, Ritika; Dhalla, Noreen; Robertson, A. Gordon; Wong, Tina; Kucherlapati, Raju S.; Fan, Cheng; Perou, Charles M.; Roach, Jeffrey; Simons, Janae V.; Fan, Huihui; Shen, Hui; Dinh, Huyen; Doddapaneni, HarshaVardhan; Lee, Sandra; Hess, Julian; Appelbaum, Elizabeth L.; Ding, Li; Fulton, Lucinda A.; Shelton, Troy; Sherman, Mark; Zmuda, Erik; Corcoran, Niall; de Carvalho, Ana C.; Vidal, Daniel O.; Hermes, Beth; Paklina, Oxana; Shabunin, Alexey; Eckman, John; Rabeno, Brenda; Bergeron, Alain; Staugaitis, Susan M.; Desjardins, Laurence; Sastre, Xavier; Bigner, Darell; McCall, Shannon; McLendon, Roger; Behera, Madhusmita; Brat, Daniel J.; Force, Seth; Eijckenboom, Wil; van Kessel, Kim E.; Zwarthoff, Ellen C.; Wullich, Bernd; Murawa, Dawid; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Bell, Debra; Flotte, Thomas; Ho, Thai; Zhang, Lizhi; Gonzalez, Ana Maria Angulo; Bondaruk, Jolanta; Gershenwald, Jeffrey; Hersey, Peter; Quinn, Michael; Stretch, Jonathan; Synott, Maria; Wilmott, James; Mirsaidi, Cyrus; Nair, Praveen; Vocke, Cathy D.; Goparaju, Chandra; Cernat, Mircea; Timmers, Henri; Schilero, Cathy; Manikhas, George; Alvaro, Domenico; Dhanasekaran, Renumathy; Duell, Rebecca; Mandt, Randy; Nguyen, Phuong; Wakely, Paul; Huland, Hartwig; Carroll, Peter R.; Chan, June M.; Fehrenbach, Ashley; Galbraith, Joseph; Knudson, Michael; Saad, Fred; Zuna, Rosemary; Feldman, Michael; Creaney, Jenette; Kendall, Sara; Bradford, Carol; Haddad, Andrea; DiPersio, John; Rubin, Mark A.; Sood, Anil K.
Cell reports (Cambridge), 04/2018, Letnik: 23, Številka: 1Journal Article
Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling their effects on the activity of transcription factors, RNA-binding proteins, and microRNAs in 5,185 TCGA tumors and 1,019 ENCODE assays. Our predictions included hundreds of candidate onco- and tumor-suppressor lncRNAs (cancer lncRNAs) whose somatic alterations account for the dysregulation of dozens of cancer genes and pathways in each of 14 tumor contexts. To demonstrate proof of concept, we showed that perturbations targeting OIP5-AS1 (an inferred tumor suppressor) and TUG1 and WT1-AS (inferred onco-lncRNAs) dysregulated cancer genes and altered proliferation of breast and gynecologic cancer cells. Our analysis indicates that, although most lncRNAs are dysregulated in a tumor-specific manner, some, including OIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergistically dysregulate cancer pathways in multiple tumor contexts. Display omitted •Hundreds of lncRNAs target cancer genes and pathways in each tumor context•lncRNA copy numbers are predictive of target cancer gene dysregulation•Most lncRNAs are predicted to be transcriptional or post-transcriptional specialists•lncRNAs are predicted to synergistically regulate proliferation pathways in cancer Chiu et al. present a pan-cancer analysis of lncRNA regulatory interactions. They suggest that the dysregulation of hundreds of lncRNAs target and alter the expression of cancer genes and pathways in each tumor context. This implies that hundreds of lncRNAs can alter tumor phenotypes in each tumor context.
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Vir: Osebne bibliografije
in: SICRIS
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