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.2016-03-142016-03-142013-12Ferdin, J., Nishida, N., Wu, X., Nicoloso, M. S., Shah, M. Y., Devlin, C., … Calin, G. A. (2013). HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts. Cell Death and Differentiation, 20(12), 1675–1687. http://doi.org/10.1038/cdd.2013.1191350-9047https://hdl.handle.net/1805/8854Recent 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.en-USConserved SequencegeneticsNeoplasmsRNA, UntranslatedArticle