2021
DOI: 10.1038/s41467-021-24196-4
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Restoration of the molecular clock is tumor suppressive in neuroblastoma

Abstract: MYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters. Ultimately, M… Show more

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Cited by 30 publications
(53 citation statements)
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References 69 publications
(82 reference statements)
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“…To specifically evaluate the lipid metabolic changes induced by MYCN, we performed targeted lipidomics in LAN5 shMYCN, MYCN3 Tet-On cells, and SK-N-AS MYCN-ER ™ cells, in which MYCN-mediated transcription is conditionally activated by 4-hydroxytamoxifen (4-OHT) 23 . Significantly altered lipids are represented in the heatmap (FDR < 0.25, Fig.…”
Section: Resultsmentioning
confidence: 99%
See 3 more Smart Citations
“…To specifically evaluate the lipid metabolic changes induced by MYCN, we performed targeted lipidomics in LAN5 shMYCN, MYCN3 Tet-On cells, and SK-N-AS MYCN-ER ™ cells, in which MYCN-mediated transcription is conditionally activated by 4-hydroxytamoxifen (4-OHT) 23 . Significantly altered lipids are represented in the heatmap (FDR < 0.25, Fig.…”
Section: Resultsmentioning
confidence: 99%
“…MRI images were analyzed and processed in Osirix (5.8.5, Pixmeo, Bernex, Switzerland), and data are expressed as tumor volume in cm 3 . Power Analysis : based on our previous studies 23 , at least six mice per group are required to reach 80% statistical power at p < 0.05 ( https://www.stat.ubc.ca/~rollin/stats/ssize/n2 ). Mice were randomized and evenly allocated into treatment groups.…”
Section: Methodsmentioning
confidence: 99%
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“…The core clock components have shown varying cross-talks with factors involved in tumorigenesis such as cell cycle, DNA damage response, cell migration, and metastasis [ 25 , 29 , 31 , 32 ]. Although it has been postulated that the clock largely functions as a tumor suppressor, individual core components show variable effects in cancers, and in some instances appear to promote cancer [ 33 36 ]. However, growing evidence strongly suggests anticancer functions of RORs specifically.…”
Section: Introductionmentioning
confidence: 99%