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 language | English |
|---|---|
| Pages (from-to) | 1812-1824 |
| Number of pages | 13 |
| Journal | Genome Research |
| Volume | 25 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2015 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors. / Hashimoto, Kosuke; Suzuki, Ana Maria; Dos Santos, Alexandre; Desterke, Christophe; Collino, Agnese; Ghisletti, Serena; Braun, Emilie; Bonetti, Alessandro; Fort, Alexandre; Qin, Xian Yang; Radælli, Enrico; Kaczkowski, Bogumil; Forrest, Alistair R R; Kojima, Soichi; Samuel, Didier; Natoli, Gioacchino; Buendia, Marie Annick; Faivre, Jamila; Carninci, Piero.
In: Genome Research, Vol. 25, No. 12, 01.12.2015, p. 1812-1824.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors
AU - Hashimoto, Kosuke
AU - Suzuki, Ana Maria
AU - Dos Santos, Alexandre
AU - Desterke, Christophe
AU - Collino, Agnese
AU - Ghisletti, Serena
AU - Braun, Emilie
AU - Bonetti, Alessandro
AU - Fort, Alexandre
AU - Qin, Xian Yang
AU - Radælli, Enrico
AU - Kaczkowski, Bogumil
AU - Forrest, Alistair R R
AU - Kojima, Soichi
AU - Samuel, Didier
AU - Natoli, Gioacchino
AU - Buendia, Marie Annick
AU - Faivre, Jamila
AU - Carninci, Piero
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84956691878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84956691878&partnerID=8YFLogxK
U2 - 10.1101/gr.191031.115
DO - 10.1101/gr.191031.115
M3 - Article
AN - SCOPUS:84956691878
VL - 25
SP - 1812
EP - 1824
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 12
ER -