The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner

  • Shangguan, Wenbing (Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University) ;
  • Lv, Xuyang (Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University) ;
  • Tian, Nan (Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University)
  • Received : 2019.05.28
  • Accepted : 2019.08.07
  • Published : 2019.11.01
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Abstract

Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of $O^6$-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.

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References

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