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Title: HINCUTs in cancer: Hypoxia-induced noncoding ultraconserved transcripts
Authors: 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.
Keywords: colorectal cancer
Ultraconserved genes
Issue Date: Dec-2013
Citation: 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. (2013-12). HINCUTs in cancer: Hypoxia-induced noncoding ultraconserved transcripts. Cell Death and Differentiation 20 (12) : 1675-1687. ScholarBank@NUS Repository.
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. © 2013 Macmillan Publishers Limited All rights reserved.
Source Title: Cell Death and Differentiation
ISSN: 13509047
DOI: 10.1038/cdd.2013.119
Appears in Collections:Staff Publications

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