Homo sapiens Raw sequence reads. Homo sapiens

High-throughput sequencing of RNA (RNA-Seq) in human cancer shows remarkable potential to simultaneously identify expression levels of protein-coding genes and long non-coding RNAs (lncRNAs). We performed RNA-Seq to investigate expression level of lncRNAs and protein-coding genes in 30 esophageal samples, including 15 esophageal squamous cell carcinoma (ESCC) tissue samples and 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE (for unsupervised random walk with each dysregulated lncRNA/PCG), to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. By this method, multiple known cancer and novel potentially functional lncRNAs were effectively identified. Quantitative reverse-transcription PCR was performed to confirm the lncRNA expression level of eight novel functional lncRNAs in an additional 120 paired ESCC patient samples. Finally, we characterized lncRNA625 as a novel ESCC regulator of cell proliferation, invasion and migration. Moreover, we identified E1A-binding protein p300 (EP300) as playing a key role in executing lncRNA625-induced transcriptional responses. These findings establish the utility of integrative bioinformatics analyses of RNA-Seq to identify cancer-associated functional lncRNAs.