Circ_0000215 aggravates cerebral ischemic vertigo by targeting miR-361-3p to promote neuroinflammation and apoptosis

J Stroke Cerebrovasc Dis. 2025 Jul;34(7):108317. doi: 10.1016/j.jstrokecerebrovasdis.2025.108317. Epub 2025 Apr 14.

Abstract

Background: Vertigo can result from cerebral ischemia (CI). Circular RNA (circRNA)'s role in CI is well-documented. This study focused on the clinical significance and mechanisms of circ_0000215 in CI-induced vertigo.

Methods: 120 CI patients and 128 control participants were enrolled. During the 90-day follow-up, 32.5 % CI patients reported vertigo. Mice models of CI-induced vertigo and a cellular OGD/R-induced HT22 model were constructed. RT-qPCR analyzed circ_0000215 and miR-361-3p expression. ROC curve analysis evaluated circ_0000215's predictive value for vertigo in CI. ELISA assessed inflammatory factor levels, while CCK-8 and flow cytometry evaluated cell proliferation and apoptosis. Dual luciferase report and RIP assays confirmed circ_0000215 binding to miR-361-3p.

Result: circ_0000215 levels were significantly elevated in CI vertigo patients, mice, and OGD-induced HT22 cells, while miR-361-3p levels were decreased. Elevated circ_0000215 diagnosed CI patients and predicted the occurrence of vertigo. Additionally, Cox regression analysis further confirmed that it is an independent risk factor for CI vertigo. Inhibiting circ_0000215 improved neurologic scores, shortened escape latency, and increased blood flow in vertigo mice, but these effects were reversed by downregulation of miR-361-3p. Moreover, decreasing circ_0000215 levels mitigated OGD/R-induced apoptosis and inflammation, yet these beneficial effects were reversed by miR-361-3p downregulation. Molecularly, circ_0000215 targets miR-361-3p.

Conclusion: Elevated circ_0000215 aids CI diagnosis and predicts vertigo. It may promote inflammation and apoptosis by targeting miR-361-3p, contributing to nerve damage in CI.

Keywords: Cerebral ischemia; Inflammation; Vertigo, circ_0000215, miR-361-3p.

MeSH terms

  • Aged
  • Animals
  • Apoptosis*
  • Brain Ischemia* / complications
  • Brain Ischemia* / genetics
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / pathology
  • Brain Ischemia* / physiopathology
  • Case-Control Studies
  • Cell Line
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neuroinflammatory Diseases* / genetics
  • Neuroinflammatory Diseases* / metabolism
  • Neuroinflammatory Diseases* / pathology
  • Neuroinflammatory Diseases* / physiopathology
  • Neurons* / metabolism
  • Neurons* / pathology
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Signal Transduction
  • Vertigo* / etiology
  • Vertigo* / genetics
  • Vertigo* / metabolism
  • Vertigo* / pathology
  • Vertigo* / physiopathology

Substances

  • MicroRNAs
  • RNA, Circular
  • MIRN361 microRNA, human
  • Inflammation Mediators