| Autor: |
Papoutsoglou, Panagiotis, Pineau, Raphaël, Leroux, Raffaële, Louis, Corentin, L'Haridon, Anaïs, Foretek, Dominika, Morillon, Antonin, Banales, Jesus M, Gilot, David, Aubry, Marc, Coulouarn, Cédric |
| Zdroj: |
EMBO Reports; Mar2024, Vol. 25 Issue 3, p1022-1054, 33p |
| 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. Synopsis: LINC00313 produces a TGFβ-regulated long non-coding RNA in cholangiocarcinoma cells. By modulating key genes of the Wnt pathway, LINC00313 transcripts fine-tune Wnt/TCF/LEF-dependent transcriptional responses and promote cholangiocarcinogenesis. LINC00313 is a TGFβ-induced non-coding gene in cholangiocarcinoma. LINC00313 enhances TCF/LEF-dependent transcriptional responses and the expression of Wnt pathway genes. Core and accessory subunits of the SWI/SNF complex interact with LINC00313 transcripts. LINC00313 expression promotes chromatin accessibility, transcription and recruitment of BRG1 to TCF7 and SULF2. LINC00313 produces a TGFβ-regulated long non-coding RNA in cholangiocarcinoma cells. By modulating key genes of the Wnt pathway, LINC00313 transcripts fine-tune Wnt/TCF/LEF-dependent transcriptional responses and promote cholangiocarcinogenesis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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