title: HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts.
abstract: 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.
authors.affiliation: 1] Department of Experimental Therapeutics, The Center for RNA Interference and Non-Coding RNAs, MD Anderson Cancer Center, The University of Texas, So Campus Research Building 3, 1881 East Road, Houston, TX 77030, USA [2] Chair of Genetics, Animal Biotechnology and Immunology, Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Groblje 3 1230, Domzale, Slovenia.
authors.forename: J
authors.initials: J
authors.lastname: Ferdin
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: M S
authors.initials: MS
authors.lastname: Nicoloso
authors.forename: M Y
authors.initials: MY
authors.lastname: Shah
authors.forename: C
authors.initials: C
authors.lastname: Devlin
authors.forename: H
authors.initials: H
authors.lastname: Ling
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Kumar
authors.forename: M A
authors.initials: MA
authors.lastname: Cortez
authors.forename: M
authors.initials: M
authors.lastname: Ferracin
authors.forename: Y
authors.initials: Y
authors.lastname: Bi
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: B
authors.initials: B
authors.lastname: Czerniak
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: T D
authors.initials: TD
authors.lastname: Schmittgen
authors.forename: M P
authors.initials: MP
authors.lastname: Voorhoeve
authors.forename: M J
authors.initials: MJ
authors.lastname: Reginato
authors.forename: M
authors.initials: M
authors.lastname: Negrini
authors.forename: R V
authors.initials: RV
authors.lastname: Davuluri
authors.forename: T
authors.initials: T
authors.lastname: Kunej
authors.forename: M
authors.initials: M
authors.lastname: Ivan
authors.forename: G A
authors.initials: GA
authors.lastname: Calin
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic
chemical_list: D004273:DNA, Neoplasm; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D022661:RNA, Untranslated; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
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