Super-enhancer-driven SLCO4A1-AS1 is a new biomarker and a promising therapeutic target in glioblastoma

Glioblastoma (GBM) is the most prevalent malignant brain tumor, yet effective treatment options remain limited. Recent studies have highlighted the role of super-enhancers (SEs) in driving oncogene expression in GBM, but the involvement of SE-associated long non-coding RNAs (lncRNAs) is not well understood. In this study, we identified SLCO4A1-AS1 as an upregulated lncRNA in GBM by analyzing datasets from GSE54791, GSE4536, and TCGA. Comprehensive analysis revealed that SLCO4A1-AS1 is significantly overexpressed in GBM and associated with poor prognosis, aggressive tumor features, and an altered tumor microenvironment.

Functional assays showed that silencing SLCO4A1-AS1 inhibited glioma cell proliferation, invasion, and self-renewal while promoting apoptosis. Epigenetic profiling indicated that SLCO4A1-AS1 expression is driven by SEs and the transcription factor SOX2. Additionally, GBM cells with high SLCO4A1-AS1 expression were more sensitive to the ERK inhibitor VX-11e, and SLCO4A1-AS1 overexpression attenuated the drug’s inhibitory effects.

Conclusion: SLCO4A1-AS1 is a super-enhancer-driven lncRNA that promotes GBM progression and modulates drug response, representing a promising therapeutic target for glioblastoma.