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Cited by 64Cancer-related molecular mechanisms researchGenomics and Chromatin DynamicsChromosomal and Genetic Variations

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

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Hashimoto, Kosuke, Suzuki, Ana Maria, Dos Santos, Alexandre, Desterke, Christophe, Collino, Agnese, Ghisletti, Serena, Braun, Emilie, Bonetti, Alessandro +11 more·2015·Genome Research
DOI 10.1101/gr.191031.115PMC PMC4665003
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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.

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  • LTR12C is among over-represented LTR subfamilies in activated RT-promoters and is pervasively activated in HBV-associated HCC.

    “These include LTR12C, which is pervasively activated in HBV-associated HCC (Supplementary Fig. 8h and Supplementary Data 7)34.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [34]

    The Results section on aberrant LTR activation reports that LTR12C was preferentially activated in HCC, with 101 elements significantly up-regulated. The stratification Results section links high LTR expression overall to viral etiology, with the highest expression mostly in HBV-positive tumors. It does not establish that LTR12C specifically is pervasively activated in HBV-associated HCC. Page numbers were not supplied in our copy. (LLM, conf=0.84)

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Sorted by citations

Authors
Hashimoto, K., Suzuki, A. M., Dos Santos, A., Desterke, C., Collino, A., Ghisletti, S., Braun, E., Bonetti, A., Fort, A., Qin, X.-Y., Radaelli, E., Kaczkowski, B., Forrest, A. R. R., Kojima, S., Samuel, D., Natoli, G., Buendia, M. A., Faivre, J., & Carninci, P.
Affiliations
  • RIKEN (JP)
  • Inserm (FR)
  • IFOM (IT)
  • KU Leuven (BE)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2015-10-28
Volume
25
Issue
12
Pages
1812-1824
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.191031.115
PMC
PMC4665003
OpenAlex
W2183798419
Cited by
64
References
2
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 1
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
Funders
  • European Union's Seventh Framework Programme (259743)
  • Japanese Ministry of Education, Culture, Sports, Science and Technology
  • French National Institute of Cancer
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
hepatocellular carcinoma, non-coding RNA, transcription start sites, c-Myc, Max, tumor recurrence, tumor differentiation
MeSH terms
ATP-Binding Cassette Sub-Family B Member 4, Animals, Cell Transformation, Neoplastic, Cell Transformation, Viral, Disease Models, Animal, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Gene Expression Regulation, Neoplastic, Mice, Knockout, ATP Binding Cassette Transporter, Subfamily B, Disease Progression, Computational Biology, Terminal Repeat Sequences, Gene Expression Profiling, RNA, Untranslated, Transcription Initiation Site, Cell Line, Tumor, Mice, Transcriptome

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