miR-222/GAS5 is involved in DNA damage and cytotoxic effects induced by temozolomide in T98G cell line

J Appl Toxicol. 2019 May;39(5):726-734. doi: 10.1002/jat.3762. Epub 2018 Dec 21.

Abstract

Temozolomide (TMZ), a therapeutic DNA alkylator that can cause lethal DNA damage in cancer cells, is widely used for the standard chemotherapy against glioblastoma. However, long-term treatment with TMZ often causes drug resistance and poor prognosis, the mechanism of which remains largely unclear. This study aimed to investigate the possible role of miR-222/GAS5 axis on DNA damage and cytotoxic effects induced by TMZ in glioblastoma cells (T98G). Data suggest that the DNA comet tail length of T98G is positively correlated with the levels of miR-222 (R2 = 0.9808, P < 0.05), and negatively correlated with the levels of GAS5 (R2 = 0.8903, P < 0.05). The optical density value of T98G is negatively correlated with the levels of miR-222 (R2 = 0.7848, P < 0.05), and positively correlated with the levels of GAS5 (R2 = 0.6886, P < 0.05). Furthermore, comet tail length and optical density value are negatively and positively correlated with the levels of O-6-methylguanine-DNA methyltransferase, respectively (R2 = 0.8462, P < 0.05; R2 = 0.7018, P < 0.05). In conclusion, miR-222/GAS5 is involved in DNA damage and cytotoxic effects induced by TMZ, which means that miR-222/GAS5 may have great potential of being used as a biomarker for screening of chemotherapeutic alkylators.

Keywords: DNA damage; T98G cell line; cytotoxicity; growth arrest-specific transcript 5 gene; miR-222; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • DNA Damage*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Temozolomide / pharmacology*

Substances

  • Antineoplastic Agents, Alkylating
  • GAS5 long non-coding RNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Temozolomide