CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors.
CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors.
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DOI：
10.1101/gr.191031.115
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发表时间：
2015-12
期刊：
影响因子：
7
通讯作者：
Carninci P
中科院分区：
文献类型：
--
作者：
Hashimoto K;Suzuki AM;Dos Santos A;Desterke C;Collino A;Ghisletti S;Braun E;Bonetti A;Fort A;Qin XY;Radaelli E;Kaczkowski B;Forrest AR;Kojima S;Samuel D;Natoli G;Buendia MA;Faivre J;Carninci P
越来越多的非编码RNA（ncRNA）与包括癌症在内的各种人类疾病有关;然而，肝细胞癌（HCC）的ncRNA转录组在很大程度上未被探索。我们使用CAGE来绘制各种类型的人类和小鼠HCC的转录起始位点，重点是远离蛋白质编码基因的ncRNA。在这里，我们报告了逆转录病毒LTR启动子，表达在健康组织，如睾丸和胎盘，但不是肝脏，被广泛激活的肝脏肿瘤。尽管HCC具有异质性，但在绝大多数样品中，LTR衍生的ncRNA的子集上调超过10倍。LTR活性高的HCC大多有病毒病因，分化程度低，复发风险高。ChIP-seq数据显示MYC和MAX与ncRNA失调相关。在全球范围内，CAGE使我们能够构建HCC的哺乳动物启动子图谱，这揭示了HCC基因组学中新的复杂性。
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.