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HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts
Journal article   Open access   Peer reviewed

HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts

J. Ferdin, N. Nishida, X. Wu, M. S. Nicoloso, M. Y. Shah, C. Devlin, H. Ling, M. Shimizu, K. Kumar, M. A. Cortez, …
Cell death and differentiation, v 20(12), pp 1675-1687
01 Dec 2013
PMID: 24037088
url
https://doi.org/10.1038/cdd.2013.119View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Biochemistry & Molecular Biology Cell Biology Life Sciences & Biomedicine Science & Technology
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.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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