Browsing by Subject "RNA, Untranslated"

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    HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts
    (Nature Publishing Group, 2013-12) Ferdin, J.; Nishida, N.; Wu, X.; Nicoloso, M. S.; Shah, M. Y.; Devlin, C.; Ling, H.; Shimizu, M.; Kumar, K.; Cortez, M. A.; Ferracin, M.; Bi, Y.; Yang, D.; Czerniak, B.; Zhang, W.; Schmittgen, T. D.; Voorhoeve, M. P.; Reginato, M. J.; Negrini, M.; Davuluri, R. V.; Kunej, T.; Ivan, M.; Calin, G. A.; Department of Medicine, IU School of Medicine
    Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs) however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named ‘hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients. We show that these T-UCRs are predominantly nuclear and that the hypoxia-inducible factor (HIF) is at least partly responsible for the induction of several members of this group. One specific HINCUT, uc.475 (or HINCUT-1) is part of a retained intron of the host protein-coding gene, O-linked N-acetylglucosamine transferase, which is overexpressed in epithelial cancer types. Consistent with the hypothesis that T-UCRs have important function in tumor formation, HINCUT-1 supports cell proliferation specifically under hypoxic conditions and may be critical for optimal O-GlcNAcylation of proteins when oxygen tension is limiting. Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category.