TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma.

Autor:	Papoutsoglou P; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France.; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, Paris, France., Pineau R; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France., Leroux R; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France., Louis C; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France., L'Haridon A; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France., Foretek D; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, Paris, France., Morillon A; ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne University, PSL University, Institut Curie, Centre de Recherche, Paris, France., Banales JM; Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, CIBERehd, Ikerbasque, San Sebastian, Spain.; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain., Gilot D; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France.; Mechanistic & Structural Biology, Discovery Sciences, R&D, AstraZeneca, SE-48183, Mölndal, Sweden., Aubry M; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France., Coulouarn C; Inserm, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) laboratory, UMR_S 1242, Centre de Lutte contre le Cancer Eugène Marquis, F-35042, Rennes, France. cedric.coulouarn@inserm.fr.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Mar; Vol. 25 (3), pp. 1022-1054. Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1038/s44319-024-00075-z
Abstrakt:	Cholangiocarcinoma is a devastating liver cancer characterized by high aggressiveness and therapy resistance, resulting in poor prognosis. Long non-coding RNAs and signals imposed by oncogenic pathways, such as transforming growth factor β (TGFβ), frequently contribute to cholangiocarcinogenesis. Here, we explore novel effectors of TGFβ signalling in cholangiocarcinoma. LINC00313 is identified as a novel TGFβ target gene. Gene expression and genome-wide chromatin accessibility profiling reveal that nuclear LINC00313 transcriptionally regulates genes involved in Wnt signalling, such as the transcriptional activator TCF7. LINC00313 gain-of-function enhances TCF/LEF-dependent transcription, promotes colony formation in vitro and accelerates tumour growth in vivo. Genes affected by LINC00313 over-expression in CCA tumours are associated with KRAS and TP53 mutations and reduce overall patient survival. Mechanistically, ACTL6A and BRG1, subunits of the SWI/SNF chromatin remodelling complex, interact with LINC00313 and affect TCF7 and SULF2 transcription. We propose a model whereby TGFβ induces LINC00313 in order to regulate the expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis. (© 2024. The Author(s).)
Databáze:	MEDLINE
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