SRS157 - An endothelial cell enriched long non-coding RNA upregulated in inflammatory bowel disease and colorectal cancer is a key regulator of endothelial cell survival, growth and angiogenesis

Abstract Inflammatory bowel disease (IBD), primarily presenting as ulcerative colitis or Crohn’s disease, is a 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 with 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 a lncRNA that is dysregulated in CAC patients and can be targeted as a therapy to block the development of CAC from IBD. We have identified an endothelial cell-enriched lncRNA, provisionally named LINC-ECER, that is upregulated in both colon cancer and IBD. Knockdown of LINC-ECER and functional assays in Human Umbilical Vein Endothelial Cells (HUVECs) and lymphatic endothelial cells (HLECs) in vitro revealed that LINC-ECER is an important regulator of endothelial cell survival, growth and angiogenesis. 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.