1. Academic Validation
  2. Implication of lncRNA ZBED3-AS1 downregulation in acquired resistance to Temozolomide and glycolysis in glioblastoma

Implication of lncRNA ZBED3-AS1 downregulation in acquired resistance to Temozolomide and glycolysis in glioblastoma

  • Eur J Pharmacol. 2022 Nov 30;175444. doi: 10.1016/j.ejphar.2022.175444.
Jiajun Dong 1 Yilong Peng 1 Minggu Zhong 1 Zhengyuan Xie 1 Zongyuan Jiang 1 Kang Wang 1 Yi Wu 2
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Jiangmen Central Hospital, Jiangmen, 529030, Guangdong, PR China.
  • 2 Department of Neurosurgery, Jiangmen Central Hospital, Jiangmen, 529030, Guangdong, PR China. Electronic address: wuyi8523@outlook.com.
Abstract

Temozolomide (TMZ) is the recommended drug for glioblastoma (GBM) treatment, but its clinical effect is restricted due to drug resistance. This research studies the effects of long non-coding RNA (lncRNA) ZBED3-AS1 and its related molecules on acquired TMZ resistance in glioblastoma (GBM). ZBED3-AS1 was identified to be downregulated in TMZ-resistant GBM cells by analyzing GSE113510 and GSE100736 datasets. ZBED3-AS1 downregulation was detected in TMZ-resistant GBM tissues and cell lines (U251/TMZ and U87/TMZ). ZBED3-AS1 knockdown promoted, whereas its overexpression suppressed TMZ resistance, viability and mobility, and glycolytic activity of TMZ-resistant cells. ZBED3-AS1 bound to Spi-1 proto-oncogene (SPI1) but did not affect its expression. Instead, it blocked SPI1-mediated transcriptional activation of thrombomodulin (THBD). SPI1 and THBD increased TMZ resistance and glycolysis in TMZ-resistant cells. Either ZBED3-AS1 overexpression or SPI1 knockdown in U87/TMZ cells blocked the growth of orthotopic and subcutaneous xenograft tumors in nude mice. In conclusion, this study demonstrates that ZBED3-AS1 downregulation and THBD activation is linked to increased TMZ resistance and glycolysis in GBM cells.

Keywords

Glioblastoma; Glycolysis; Long non-coding RNA ZBED3-AS1; SPI1; Temozolomide resistance.

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