A HOTAIR-associated super-enhancer orchestrates glioblastoma malignancy via MEST

Glioblastoma (GBM) is one of the most malignant primary brain tumors, and factors governing its progression are not fully characterized. Recent research suggests that the long non-coding RNA (lncRNA) HOTAIR and super-enhancers (SEs) contribute significantly to GBM progression. Here, we performed TCGA data analysis revealing that high HOTAIR expression in GBM is associated with poor prognosis. Conversely, HOTAIR KD decreased proliferation, colony formation and invasion of GBM cells. Furthermore, RNA-seq analysis identified differentially expressed genes (DEGs) in GBM cells related to cell growth and adhesion. Using an integrated approach, we also identify MEST as a HOTAIR-associated SE target gene. Intriguingly, MEST suppression in GBM cells phenocopied HOTAIR KD, as evidenced by reduced cell proliferation and invasion, whereas MEST overexpression counteracted effects of HOTAIR depletion. Moreover, Chromosome Conformation Capture (3C) technique-based PCR confirmed reduced interaction between HOTAIR-associated SEs and target genes after HOTAIR KD. This study reveals a novel regulatory mechanism governing GBM, offering promising directions for clinical interventions.