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Introduction Inflammatory bowel diseases (IBD), primarily ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory condition of the gut leading to increased risk of developing colorectal cancer (CRC). IBD-induced CRC, termed colitis-associated cancer (CAC), with earlier onset and higher mortality rate than sporadic CRC, follows a flat inflammation-to-dysplasia-to-carcinoma path of tumorigenesis supported by a mixed immune and stromal cell-rich tumour microenvironment. Long non-coding RNAs (lncRNAs), a class of non-protein-coding RNA molecules more than 200 nucleotides long are expressed in a high tissue- and disease-specific manner and may represent promising targets for therapy. We aimed to identify lncRNA dysregulated in CAC patients which can be targeted to block the progression of IBD to CAC.Methods We conducted lncRNA microarray profiling (Arraystar) in CRC tumours, UC-active and CD patient and normal adjacent colonic tissues to identify lncRNA dysregulated in CRC and IBD patients. Publicly available bulk RNA sequencing (RNAseq) data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Ontology (GEO) were analysed to validate the expression of specific lncRNAs in CRC and IBD and identify co-regulated genes. RT-qPCR was performed in RNA from 10 CRC cell lines, immortalised normal colonic cell lines and primary endothelial cells (EC) (HUVECs, HLECs and HIMECs). Primary ECs were transfected or lentivirally transduced to knock down (KD) and overexpress (OE) the lncRNA of interest. Functional assays were performed to investigate the effects of lncRNA KD or OE including on cell growth, angiogenesis, cell migration and endogenous reactive oxygen species (ROS) production. RNAseq was performed to assess the effects of the lncRNA on global gene expression and RNAscope in situ hybridisation was employed to probe its localisation in colonic tissues from IBD, CRC and CAC patients.Results We identified an endothelial cell-enriched lncRNA, provisionally named LINC-ECER (Long Intergenic Non-Coding Endothelial Cell Enriched RNA), that is upregulated in both colon cancer and IBD and co-expressed with genes associated with inflammation, angiogenesis and extracellular matrix (ECM) organisation. While LINC-ECER is not expressed in CRC or colonic epithelial cell lines, it is markedly expressed in all primary EC lines tested. Functional and transcriptomic analyses using primary ECs and diseased tissues revealed that LINC-ECER is an important regulator of EC survival, growth, ROS production and tube formation.Conclusions Overall, our data proposes that LINC-ECER is a critical regulator of endothelial cell properties and can be targeted in IBD patients to specifically block angiogenesis and prevent CAC development.