Work

Post-transcriptional control of HIF-1α by MBNL1 restrains hypoxia-driven stemness in GBM

Year: 2025

Type: article

Abstract: MBNL1 binds the HIF-1α 3'UTR to promote rapid mRNA decay, thereby limiting HIF-1 activity and hypoxia-induced stemness in glioblastoma. Using patient-derived glioma stem cells, we show that MBNL1 loss stabilizes HIF-1α mRNA and increases HIF-1α protein, HRE reporter activity, and target gene expression under hypoxia; MBNL1 knockout also prolongs target gene expression after reoxygenation, indicating enhanced hypoxia "memory." MBNL1 depletion markedly elevates stemness markers (KLF4, SOX2, GLI1) and clonogenic growth, and re-expression of MBNL1 reverses these effects. These results identify a post-transcriptional MBNL1-HIF1α axis that controls hypoxia signaling and stemness, with implications for GBM therapy.

Source: Neoplasia

DOI: 10.1016/j.neo.2025.101262