Cerebrospinal fluid exosomal miR-152-3p predicts the occurrence of subarachnoid haemorrhage and regulates vascular smooth muscle cell dysfunction

Introduction
Ruptured intracranial aneurysm (RA) can lead to subarachnoid haemorrhage (SAH). This study was to explore the predictive value of cerebrospinal fluid (CSF) derived exosome miR-152-3p and its regulatory role in the human vascular smooth muscle cells (HVSMCs).

Material and methods
Real-time quantitative polymerase reaction was carried out to detect CSF exosome miR-152-3p in 66 patients with unruptured intracranial aneurysms (UA), 69 patients with RA, and 68 patients with hydrocephalus. Clinical predictive value of SAH occurrence was assessed using receiver operating characteristic curve (ROC) and logistics regression analysis. Cell Counting Kit-8 and Transwell were employed to detect the proliferation and migration of HVSMCs. The binding relationship between miR-152-3p and PTEN was confirmed by the dual-luciferase reporter assay.

Results
Compared with hydrocephalus, exosome miR-152-3p was lower in patients with intracranial aneurysms, and among them, RA was lower than in patients with UA (p < 0.001). ROC confirmed that exosome miR-152-3p not only distinguishes patients with UA from patients with hydrocephalus but also predicts SAH in patients with intracranial aneurysms. Logistic regression analysis showed that miR-152-3p (OR = 0.039, 95% CI = 0.015-0.106, p < 0.001) and aneurysm size (OR = 2.701, 95% CI = 1.045-6.890, p = 0.040) were independent predictors of progression for UA to RA. Increased miR-152-3p inhibited the proliferation and migration of HVSMCs. PTEN was the direct target gene of miR-152-3p, which was elevated in CSF-derived exosomes and negatively correlated with miR-152-3p levels.

Conclusions
Our study confirmed that the CSF-derived exosome miR-152-3p was a feasible predictor of SAH and was involved in the dysfunction of HVSMCs.