Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294

J Biosci. 2020:45:101.

Abstract

Glioma is one of the most aggressive forms of brain tumor and is hallmarked by high rate of mortality, metastasis and drug resistance. Herein, we explore the role of circular RNA (circRNA) hsa_circ_0000936 in the resistance of glioma cells to temozolomide (TMZ). In this study, Relative changes in gene expression levels were compared using qRT-PCR. The role of hsa_circ_0000936 was characterized by cell count kit -8 assay and flow cytometry. Luciferase reporter assay was carried out for target validation.We found that hsa_circ_0000936 was upregulated in glioma tissues as compared to their adjacent normal tissues. Increased expression of hsa_circ_0000936 was found in the glioma tissues of patients showing resistance to TMZ compared with that of patients showing sensitivity to TMZ. The upregulation of hsa_circ_0000936 was also confirmed in TMZresistant glioma cells. miR-1294 was downregulated in TMZ-resistant glioma cells and identified as a direct target of hsa_circ_0000936. Downregulation of hsa_circ_0000936 increased the sensitivity of TMZ-resistant glioma cells towards TMZ. Moreover, restoration of miR-1294 could abrogate the promoting effect of hsa_circ_0000936 on TMZ resistance in TMZ-resistant glioma cells. In conclusion, downregulation of hsa_circ_0000936 sensitizes TMZ-resistant glioma cells to TMZ by sponging miR-1294, suggesting that hsa_circ_0000936 may be a potential target for overcoming the resistance of glioma cells to TMZ.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / surgery
  • Humans
  • Inhibitory Concentration 50
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • RNA, Circular / antagonists & inhibitors
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Temozolomide / pharmacology*

Substances

  • Antineoplastic Agents, Alkylating
  • MIRN1294 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • Luciferases
  • Temozolomide