GSE106432
TP63-driven super-enhancer-associated LINC01503 promotes the malignancy of esophageal squamous cell carcinoma (4C-Seq)
Background & Aims: Lineage-specific expression of long non-coding RNAs (lncRNAs)  has been observed recently. However, the underlying mechanism of such specific  transcription regulation is unclear. The aim of this study is to identify squamous cell carcinoma (SCC) lineage-specific lncRNAs and to investigate the mechanisms for their  expression and function.  Methods: Expression characteristics and functions of four candidate SCC-specific  lncRNAs were explored. qRT-PCR assays were employed to measure the expression  of LINC01503 in 113 tumor/normal matched esophageal SCC (ESCC) cases and its  association with survival was determined. The mechanisms underlying LINC01503  function and regulation in ESCC cells were examined using molecular biological  methods.  Results: Using SCC as a model, we identified a novel super-enhancer (SE)-driven  lncRNA, LINC01503, which was uniquely expressed in SCCs such as those from  esophagus (ESCC) and head and neck (HNSC). LINC01503 was up-regulated in  SCCs and its high expression correlated with poor clinical outcomes. SCC master  transcriptional factor TP63 directly bound to a SE at LINC01503 locus and activated its  transcription. LINC01503 exhibited strong oncogenic functions in ESCC cell models  both in vitro and in vivo. ERK2 and EBP-1 were identified as interacting proteins  mediating the effects of LINC01503. Specifically, LINC01503 protected ERK2 from  dephosphorylation by DUSP-6, leading to the activation of ERK/MAPK pathway.  Similarly, LINC01503 interfered the interaction between EBP-1 and PI3K p85,  enhancing Akt signaling pathway.  Conclusions: These results demonstrated that LINC01503 is a lineage-specific  oncogene in ESCC, which may serve as a potential biomarker and therapeutic target  for SCC patients. Overall design: 4C sequencing of TE7 Esophageal Squamous Cell Carcinoma Cell Line