#IDIBELLseminars: TGFbeta-induced circular RNAs in cholangiocarcinoma: mechanisms and biomarkers

Cholangiocarcinoma (CCA) is a deadly cancer worldwide and opening the field to new concepts is required to improve the survival of patients. Recently, circular RNAs (circRNAs) emerged in the field of cancer but their role in CCA onset and progression has been poorly investigated. Here, we identified circRNAs regulated by Transforming Growth Factor beta (TGFb) in CCA cell lines, including circRNA-TB1, which expression in CCA tumors is predictive of a poor survival. Functional studies demonstrated that circRNA-TB1 increases tumor cell proliferation, migration, and resistance to gemcitabine-induced apoptosis, and promotes tumor growth in mice. Mechanistically, circRNA-TGFB1 may act as a competitive RNA sponge for miR-338, a tumor suppressor microRNA. More interestingly, circRNA-TB1 is detected in extra-cellular vesicles isolated from the serum of patients with CCA, where it is predictive of a poor prognosis, opening the field to innovative biomarkers.

Hosted by Isabel Fabregat – TGF-beta and cancer Group

Dr Cédric Coulouarn is a research director at Inserm in Rennes. After a PhD in molecular biology (Univ. Rouen, 2004) and a 5-year experience at the National Cancer Institute (NIH, Bethesda, USA), he acquired expertise in the field of liver cancer with a specific focus on TGF-beta signaling, non-coding RNAs and functional genomics. He obtained a permanent position at Inserm in 2012. Dr Coulouarn is a member of European association for the Study of the Liver (EASL), International Liver Cancer Association (ILCA) and European Network for the Study of Cholangiocarcinoma (ENSCCA). His team is currently investigating the role and the clinical relevance of TGF-beta-regulated lncRNA and circRNA in hepatocellular carcinoma and cholangiocarcinoma.