ArticleCell proliferation2023
A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.
Article in Cell proliferation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 4 citations in OpenAlex.
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- Binding of berberine to PEBP1 synergizes with sorafenib to induce the ferroptosis of hepatic stellate cells.Amino acids · 2023Article
- A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.Cell proliferation · 2023Article
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
objectivesElimination of brain tumour initiating cells (BTICs) is important for the good prognosis of malignant brain tumour treatment. To develop a novel strategy targeting BTICs, we studied NR2E1(TLX) involved self-renewal mechanism of BTICs and explored the intervention means. MATERIALS AND
methodsNR2E1 and its interacting protein-LSD1 in BTICs were studied by gene interference combined with cell growth, tumour sphere formation, co-immunoprecipitation and chromatin immunoprecipitation assays. NR2E1 interacting peptide of LSD1 was identified by Amide Hydrogen/Deuterium Exchange and Mass Spectrometry (HDX-MS) and analysed by in vitro functional assays. The in vivo function of the peptide was examined with intracranial mouse model by transplanting patient-derived BTICs.
resultsWe found NR2E1 recruits LSD1, a lysine demethylase, to demethylate mono- and di-methylated histone 3 Lys4 (H3K4me/me2) at the Pten promoter and repress its expression, thereby promoting BTIC proliferation. Using Amide Hydrogen/Deuterium Exchange and Mass Spectrometry (HDX-MS) method, we identified four LSD1 peptides that may interact with NR2E1. One of the peptides, LSD1-197-211 that locates at the LSD1 SWIRM domain, strongly inhibited BTIC proliferation by promoting Pten expression through interfering NR2E1 and LSD1 function. Furthermore, overexpression of this peptide in human BTICs can inhibit intracranial tumour formation.
conclusionPeptide LSD1-197-211 can repress BTICs by interfering the synergistic function of NR2E1 and LSD1 and may be a promising lead peptide for brain tumour therapy in future.
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