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Original Article

Korean J Physiol Pharmacol 2019; 23(6): 475-482

Published online November 1, 2019 https://doi.org/10.4196/kjpp.2019.23.6.475

Copyright © The Korean Journal of Physiology & Pharmacology.

FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O6-methylguanine-DNA methyltransferase-dependent manner

Wenbing Shangguan, Xuyang Lv, and Nan Tian*

Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China

Correspondence to:Nan Tian
E-mail: tiannanlux@126.com

Received: May 28, 2019; Revised: July 30, 2019; Accepted: August 7, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 O6-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.

Keywords: Drug Resistance, Glioma, Long-noncoding RNA, Methylation, Temozolomide