Circ_0005198 enhances temozolomide resistance of glioma cells through miR-198/TRIM14 axis

Aging (Albany NY). 2020 Dec 9;13(2):2198-2211. doi: 10.18632/aging.202234. Epub 2020 Dec 9.


Circular RNAs (circRNAs) are associated with chemoresistance in many cancers. However, the function of circ_0005198 in the temozolomide (TMZ) resistance of glioma has not been well elucidated. Here, we demonstrated that circ_0005198 was considerably up-regulated in glioma tissues, serum samples and TMZ-resistant glioma cells. Silencing of circ_0005198 restrained TMZ resistance, restricted the proliferation and facilitated the apoptosis of TMZ-resistant glioma cells. MiR-198 could be sponged by circ_0005198, and we demonstrated that the effect of circ_0005198 on the progression of TMZ-resistant glioma cells was attributed to the inhibition of miR-198 activity. Moreover, TRIM14 was a target of miR-198 and silencing of TRIM14 hindered TMZ resistance and suppressed the progression of TMZ-resistant glioma cells, while TRIM14 over-expression rescued the inhibiting effect of miR-198 over-expression. We conclude that circ_0005198-miR-198-TRIM14 regulatory pathway is critical to TMZ resistance of glioma.

Keywords: TMZ resistance; TRIM14; circ_0005198; glioma; miR-198.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Temozolomide / pharmacology*
  • Temozolomide / therapeutic use
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*
  • Up-Regulation / drug effects


  • Antineoplastic Agents, Alkylating
  • Intracellular Signaling Peptides and Proteins
  • MIRN198 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • TRIM14 protein, human
  • Tripartite Motif Proteins
  • Temozolomide