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LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [ChIP-seq]

ABSTRACT: Glioblastoma (GBM) is characterized by a high degree of hypoxia. Hypoxia-inducible factors (HIFs) modulate glioma stem-like cell (GSC) responses to hypoxia and promote GBM progression, therapeutic resistance, and recurrence. Here we identify a new transcript of the long non-coding RNA LUCAT1 and show that it reinforces HIF1⍺ signaling in GSCs under hypoxia. LUCAT1 expression is highly induced under hypoxia in GBM and GSCs in a HIF1⍺-dependent manner. High LUCAT1 expression in human GBM correlates with increased aggression and poor survival. Mechanistically, LUCAT1 associates with chromatin and modulates interaction between HIF1⍺ and coactivator CBP to hypoxia response elements (HREs) to drive HIF1⍺-target gene expression under hypoxia. Thus, LUCAT1 acts as a positive feedback factor to augment HIF1⍺ signaling under hypoxic stress in GSCs. Loss of LUCAT1 reduces tumor growth and prolongs mouse survival in xenograft models of GBM. Our findings provide new insights into how GSCs regulate gene expression under hypoxia and identify LUCAT1 as therapeutic target in GBM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255502 | GEO | 2024/03/12

REPOSITORIES: GEO

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LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [RNA-seq]

Project description:Glioblastoma (GBM) is characterized by a high degree of hypoxia. Hypoxia-inducible factors (HIFs) modulate glioma stem-like cell (GSC) responses to hypoxia and promote GBM progression, therapeutic resistance, and recurrence. Here we identify a new transcript of the long non-coding RNA LUCAT1 and show that it reinforces HIF1⍺ signaling in GSCs under hypoxia. LUCAT1 expression is highly induced under hypoxia in GBM and GSCs in a HIF1⍺-dependent manner. High LUCAT1 expression in human GBM correlates with increased aggression and poor survival. Mechanistically, LUCAT1 associates with chromatin and modulates interaction between HIF1⍺ and coactivator CBP to hypoxia response elements (HREs) to drive HIF1⍺-target gene expression under hypoxia. Thus, LUCAT1 acts as a positive feedback factor to augment HIF1⍺ signaling under hypoxic stress in GSCs. Loss of LUCAT1 reduces tumor growth and prolongs mouse survival in xenograft models of GBM. Our findings provide new insights into how GSCs regulate gene expression under hypoxia and identify LUCAT1 as therapeutic target in GBM.

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HIF1 is a master regulator of the adaptive gene expression to hypoxia.

Project description:Total 23 samples were derived from [1] HUVEC treated in the absence (0h) or presence of hypoxia (1, 2, 4, 8, 12, and 24 hrs) to determine hypoxia-regulated gene in endothelial cells, [2] control siRNA or HIF1α siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [3] control siRNA or KDM3A siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [4] ChIP-seq data for HIF1 binding sites and histone modifications under normoxia and hypoxia in endothelial cells.

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2015-12-11 | E-GEOD-66956 | biostudies-arrayexpress

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