CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors

Kosuke Hashimoto, Ana Maria Suzuki, Alexandre Dos Santos, Christophe Desterke, Agnese Collino, Serena Ghisletti, Emilie Braun, Alessandro Bonetti, Alexandre Fort, Xian Yang Qin, Enrico Radælli, Bogumil Kaczkowski, Alistair R R Forrest, Soichi Kojima, Didier Samuel, Gioacchino Natoli, Marie Annick Buendia, Jamila Faivre, Piero Carninci

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1812-1824
Number of pages13
JournalGenome Research
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Hashimoto, K., Suzuki, A. M., Dos Santos, A., Desterke, C., Collino, A., Ghisletti, S., Braun, E., Bonetti, A., Fort, A., Qin, X. Y., Radælli, E., Kaczkowski, B., Forrest, A. R. R., Kojima, S., Samuel, D., Natoli, G., Buendia, M. A., Faivre, J., & Carninci, P. (2015). CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors. Genome Research, 25(12), 1812-1824. https://doi.org/10.1101/gr.191031.115