Recurrently deregulated lncRNAs in hepatocellular carcinoma.
Yang YangLei ChenJin GuHanshuo ZhangJiapei YuanQiuyu LianGuishuai LvSiqi WangYang WuYu-Cheng T YangDongfang WangYang LiuJing TangGuijuan LuoYang LiLong HuXinbao SunDong WangMingzhou GuoQiaoran XiJianzhong XiHongyang WangMichael Q ZhangZhi John LuPublished in: Nature communications (2017)
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Keyphrases
- genome wide identification
- genome wide analysis
- network analysis
- copy number
- rna seq
- dna methylation
- electronic health record
- immune response
- genome wide
- big data
- single cell
- end stage renal disease
- transcription factor
- high throughput
- pulmonary embolism
- newly diagnosed
- gene expression
- induced apoptosis
- ejection fraction
- peritoneal dialysis
- prognostic factors
- mass spectrometry
- systematic review
- signaling pathway
- dendritic cells
- long non coding rna
- cell proliferation
- binding protein
- pi k akt