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

Glioblastoma (GBM) is the most common intracranial malignancy, but current treatment options are limited. Super-enhancers (SEs) have been found to drive the expression of key oncogenes in GBM. However, the role of SE-associated long non-coding RNAs (lncRNAs) in GBM remains poorly understood. Here, we screened for an up-regulated lncRNA-SLCO4A1-AS1 expressed in GBM by analyzing data from GSE54791, GSE4536 and TCGA. We systematically analyzed its relationship with clinical characteristics, prognosis, epigenetics, tumor microenvironment (TME), biological functions, and transcription factors. We found that SE-driven SLCO4A1-AS1 was significantly upregulated in GBM and correlated with poor prognosis. Knockdown of SLCO4A1-AS1 decreased glioma cell proliferation, invasive ability, self-renewal ability, and increased apoptosis. Epigenetic analysis revealed that SOX2 and SE could drive SLCO4A1-AS1 expression. In vitro experiments further demonstrated that GBM cells with high SLCO4A1-AS1 expression were more sensitive to VX-11e, and overexpression of SLCO4A1-AS1 could reverse the inhibitory effect of VX-11e on GBM cells. In conclusion, this study revealed that SE-driven SLCO4A1-AS1 may be a potential therapeutic target in GBM.