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Etude de la voie TGFβ dans le cholangiocarcinome intrahépatique : implication des ARN longs non-codants

Abstract : Intrahepatic cholangiocarcinoma (ICC) is a primary liver tumor developed from bile ducts. ICC prognosis is poor with current treatments that slightly increase patient survival. ICC carcinogenesis is complex and involves multiple signaling pathways including TGFβ pathway. Our hypothesis relies on the involvement of long non-coding RNA (lncRNA) as mediators of TGFβ pathway in the development of ICC. The aim of the study was to identify and to characterize TGFβ regulated lncRNA as ICC potential diagnostic or prognostic biomarkers. We identified a specific transcriptomic signature after stimulation of ICC cell lines with TGFβ. Among the novel TGFβ target genes, several lncRNAs were identified including CASC15 renamed TLINC standing for TGFβ-induced long intergenic non-coding RNA. TLINC may play a role in the remodeling of an inflammatory microenvironment involved in ICC carcinogenesis, including the regulation of IL8. This role could be exerted by the interaction with other lncRNAs already identified in the ICC e.g. NEAT1. TLINC is overexpressed in human ICC tumors and may represent a relevant diagnostic biomarker. Circular isoforms of TLINC found in tumors may be detectable in serum and be noninvasive biomarkers. Transcriptomic analysis of tumors from a cohort of patients divided into 2 prognostic groups identified a lncRNAs signature predictive for survival. LncRNA ANRIL, already known to be upregulated in other cancers, is one of the lncRNAs that could be a prognostic biomarker in ICC.
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Submitted on : Friday, December 20, 2019 - 12:04:07 PM
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  • HAL Id : tel-02421163, version 1


Aude Merdrignac. Etude de la voie TGFβ dans le cholangiocarcinome intrahépatique : implication des ARN longs non-codants. Biochimie, Biologie Moléculaire. Université Rennes 1, 2019. Français. ⟨NNT : 2019REN1B020⟩. ⟨tel-02421163⟩



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