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000294580 1001_ $$aSchwarzmueller, Laura J$$b0
000294580 245__ $$aIdentifying colorectal cancer-specific vulnerabilities in the Wnt-driven long non-coding transcriptome.
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000294580 520__ $$aAberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved.In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome and exploit essential molecules as novel therapeutic targets.We used global run-on sequencing to define β-catenin-regulated long non-coding RNAs (lncRNAs) in CRC. CRISPRi dropout screens were subsequently used to establish the functional relevance of a subset of these lncRNAs for long-term expansion of CRC.We uncovered that LINC02418 is essential for cancer cell clonogenic outgrowth. Mechanistically, LINC02418 regulates MYC expression levels to promote CRC stem cell functionality and prevent terminal differentiation. Furthermore, we developed effective small interfering RNA (siRNA)-based therapeutics to target LINC02418 RNA in vivo.We propose that cancer-specific Wnt-regulated lncRNAs provide novel therapeutic opportunities to interfere with the Wnt pathway, which has so far defied effective pharmacological inhibition.
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000294580 650_7 $$2Other$$acolorectal cancer
000294580 7001_ $$aAdam, Ronja S$$b1
000294580 7001_ $$aMoreno, Leandro F$$b2
000294580 7001_ $$aNijman, Lisanne E$$b3
000294580 7001_ $$aLogiantara, Adrian$$b4
000294580 7001_ $$aEleonora, Steven$$b5
000294580 7001_ $$aBril, Oscar$$b6
000294580 7001_ $$aVromans, Sophie$$b7
000294580 7001_ $$ade Groot, Nina E$$b8
000294580 7001_ $$aGiugliano, Francesca Paola$$b9
000294580 7001_ $$0P:(DE-He78)dc4f734225935c3650fde7619c82ed92$$aStepanova, Ekaterina$$b10
000294580 7001_ $$aMuncan, Vanesa$$b11
000294580 7001_ $$aElbers, Clara C$$b12
000294580 7001_ $$aLenos, Kristiaan J$$b13
000294580 7001_ $$aZwijnenburg, Danny A$$b14
000294580 7001_ $$avan Eijndhoven, Monique A J$$b15
000294580 7001_ $$aPegtel, Dirk Michiel$$b16
000294580 7001_ $$avan Neerven, Sanne M$$b17
000294580 7001_ $$0P:(DE-He78)4af0380446b05b5f1995502016151a1b$$aLoayza-Puch, Fabricio$$b18
000294580 7001_ $$aDadali, Tulin$$b19
000294580 7001_ $$aBroom, Wendy J$$b20
000294580 7001_ $$aMaier, Martin A$$b21
000294580 7001_ $$aKoster, Jan$$b22
000294580 7001_ $$00000-0002-3253-2971$$aVermeulen, Louis$$b23
000294580 7001_ $$00000-0002-6086-5984$$aLéveillé, Nicolas$$b24
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