https://orcid.org/0000-0003-4075-9460
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Ying Zhang, Kadie Hudson, Roger Abounader, Unraveling the hypoxic puzzle: LncRNA LUCAT1 drives glioblastoma in cooperation with HIF1α, Neuro-Oncology, Volume 26, Issue 8, August 2024, Pages 1402–1404, https://doi.org/10.1093/neuonc/noae096
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Hypoxia and glioblastoma stem cells (GSCs) are pivotal factors that drive the progression and therapeutic resistance of glioblastoma (GBM), the most common and aggressive primary brain tumor. Hypoxia, defined as the lack of sufficient oxygen in tissues, promotes tumor aggressiveness, metastasis, and therapeutic resistance.1 GSCs often reside in hypoxic niches where they are protected from radiation and chemotherapies, thus creating a reservoir of tumor cells that facilitate tumor recurrence. Hypoxic environments foster GSC maintenance through the activity of hypoxia-inducible factors (HIFs) that promote the expression of stem cell regulators like Nanog and Oct4.2 Long noncoding RNAs (lncRNAs) are a large and diverse class of non-protein-coding transcripts that are longer than 200 nucleotides and that act as important regulators of biological and pathological functions, including in cancer and GBM.3 While lncRNAs are known regulators of cell fate and cancer progression, their precise role in GSC maintenance in hypoxic GBM environments is not well understood.4,5 A recent study by Huang et al. that was published in Neuro-Oncology addresses this issue and uncovers a new role for lncRNA lung-cancer-associated transcript-1 (LUCAT1) in promoting GSC maintenance under hypoxic conditions to promote GBM growth.6 The study revealed that LUCAT1 is induced by hypoxia in a HIF1α-dependent manner. LUCAT1, in turn, promoted HIF1α transcriptional activity by directly binding to HIF1α and forming a complex with its co-activator CBP to enhance the expression of HIF1α target genes (Figure 1). This positive feedback loop facilitated GSC adaptation to hypoxic conditions and promoted GBM growth.
