Circ-VPS18 Knockdown Enhances TMZ Sensitivity and Inhibits Glioma Progression by MiR-370/RUNX1 Axis

Weimin Li1, Qingqin Ma2, Quan Liu3

  • 1Central Neurosurgery Group of Encephalopath, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, 130021, Changchun, Jilin, China.

Insights

This study reveals that circ-VPS18 promotes temozolomide (TMZ) resistance in glioma by sponging miR-370, which targets RUNX1. Reducing circ-VPS18 enhances TMZ sensitivity and inhibits glioma progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioma is a common brain tumor often treated with temozolomide (TMZ).
  • Acquired resistance to TMZ significantly complicates glioma treatment and necessitates understanding underlying mechanisms.
  • Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, including glioma.

Purpose of the Study:

  • To investigate the role of circ-VPS18 in temozolomide (TMZ) resistance in glioma.
  • To elucidate the molecular mechanism by which circ-VPS18 influences TMZ sensitivity and glioma progression.
  • To explore the potential of targeting the circ-VPS18/miR-370/RUNX1 axis for overcoming TMZ resistance.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect expression levels of circ-VPS18, miR-370, RUNX1, MRP1, and MDR1.
  • Cell counting kit-8 (CCK-8), flow cytometry, and transwell assays assessed the functional effects of circ-VPS18 knockdown on TMZ sensitivity and glioma cell behaviors.
  • Dual-luciferase reporter assays and in vivo tumor formation assays were employed to validate molecular interactions and therapeutic efficacy.

Main Results:

  • Circ-VPS18 and RUNX1 expression were upregulated, while miR-370 was downregulated in glioma cells and tissues, particularly in TMZ-resistant samples.
  • Knockdown of circ-VPS18 significantly enhanced TMZ sensitivity, induced apoptosis, and suppressed viability, migration, and invasion of glioma cells.
  • Circ-VPS18 acts as a molecular sponge for miR-370, and miR-370 targets RUNX1, establishing a regulatory axis that impacts TMZ resistance and glioma progression.

Conclusions:

  • Circ-VPS18 promotes TMZ resistance in glioma by sponging miR-370, leading to increased RUNX1 expression.
  • Targeting circ-VPS18 offers a potential therapeutic strategy to overcome temozolomide resistance in glioma.
  • The circ-VPS18/miR-370/RUNX1 pathway provides novel insights into glioma treatment resistance.

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