CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors
- Kosuke Hashimoto1,
- Ana Maria Suzuki1,
- Alexandre Dos Santos2,3,
- Christophe Desterke2,3,
- Agnese Collino4,
- Serena Ghisletti4,
- Emilie Braun2,3,
- Alessandro Bonetti1,
- Alexandre Fort1,
- Xian-Yang Qin5,
- Enrico Radaelli6,
- Bogumil Kaczkowski1,
- Alistair R.R. Forrest1,
- Soichi Kojima5,
- Didier Samuel2,3,
- Gioacchino Natoli4,
- Marie Annick Buendia2,3,
- Jamila Faivre2,3,7 and
- Piero Carninci1
- 1RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, 230-0045 Japan;
- 2INSERM, U1193, Paul-Brousse Hospital, Hepatobiliary Centre, 94800 Villejuif, France;
- 3Université Paris Saclay, Faculté de Médecine Le Kremlin Bicêtre, 94800 Villejuif, France;
- 4European Institute of Oncology (IEO), Department of Experimental Oncology, IFOM-IEO Campus, 20139 Milan, Italy;
- 5RIKEN Center for Life Science Technologies, Division of Bio-function Dynamics Imaging, Wako, Saitama, 351-0198, Japan;
- 6VIB Center for the Biology of Disease, KU Leuven Center for Human Genetics, B-3000 Leuven, Belgium;
- 7Assistance Publique-Hôpitaux de Paris (AP-HP), Pôle de Biologie Médicale, Paul-Brousse Hospital, 94800 Villejuif, France
- Corresponding authors: carninci{at}riken.jp, jamila.faivre{at}inserm.fr
Abstract
An increasing number of noncoding RNAs (ncRNAs) have been implicated in various human diseases including cancer; however, the ncRNA transcriptome of hepatocellular carcinoma (HCC) is largely unexplored. We used CAGE to map transcription start sites across various types of human and mouse HCCs with emphasis on ncRNAs distant from protein-coding genes. Here, we report that retroviral LTR promoters, expressed in healthy tissues such as testis and placenta but not liver, are widely activated in liver tumors. Despite HCC heterogeneity, a subset of LTR-derived ncRNAs were more than 10-fold up-regulated in the vast majority of samples. HCCs with a high LTR activity mostly had a viral etiology, were less differentiated, and showed higher risk of recurrence. ChIP-seq data show that MYC and MAX are associated with ncRNA deregulation. Globally, CAGE enabled us to build a mammalian promoter map for HCC, which uncovers a new layer of complexity in HCC genomics.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.191031.115.
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Freely available online through the Genome Research Open Access option.
- Received February 14, 2015.
- Accepted September 30, 2015.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
