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

in Scientific reports by Yibo Wu, Fang Li, Chen Yang, Xuehai Zhang, Zhiwei Xue, Yanfei Sun, Xiaoying Lin, Xuemeng Liu, Zhimin Zhao, Bin Huang, Qibing Huang, Xingang Li, Mingzhi Han

TLDR

  • This study revealed that SE-driven SLCO4A1-AS1 may be a potential therapeutic target in GBM, as it is upregulated in the disease and associated with poor prognosis.

Abstract

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.

Overview

  • The study investigates the role of super-enhancer (SE) associated long non-coding RNAs (lncRNAs) in glioblastoma (GBM).
  • The researchers analyzed data from GSE54791, GSE4536, and TCGA to identify an up-regulated lncRNA, SLCO4A1-AS1, in GBM.
  • The study aims to understand the relationship between SLCO4A1-AS1 and clinical characteristics, prognosis, epigenetics, tumor microenvironment, biological functions, and transcription factors.

Comparative Analysis & Findings

  • The study 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, while in vitro experiments showed that high SLCO4A1-AS1 expression made GBM cells more sensitive to VX-11e.

Implications and Future Directions

  • The study suggests that SE-driven SLCO4A1-AS1 may be a potential therapeutic target in GBM.
  • Future studies should aim to further validate the findings and investigate the mechanisms by which SLCO4A1-AS1 contributes to GBM development and progression.
  • Elucidating the epigenetic regulation of SLCO4A1-AS1 and identifying potential biomarkers or therapeutic strategies for GBM treatment are also promising research directions.
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