Work

CircHIPK3 regulates TGF-β1/smad3 signaling in communicating hydrocephalus after intraventricular hemorrhage by sponging miR-30a-3p via ACT1

Year: 2026

Type: article

Abstract: While circRNAs have been demonstrated to play critical roles in various neurological disorders, their functional mechanisms in post-intraventricular hemorrhage (IVH) communicating hydrocephalus remain poorly understood. Here we report a circular RNA, circular RNA homeodomain interacting protein kinase 3 (circHIPK3), significantly upregulated in meningeal tissues of IVH rat models. Knockdown of circHIPK3 markedly attenuated meningeal fibrosis, reduced ventricular dilation, and improved neurological function in IVH rats. Using both IVH rat models and thrombin-induced astrocyte cell lines, we validated the functional role of circHIPK3 in the pathogenesis of IVH-induced communicating hydrocephalus. Mechanistically, circHIPK3 functions as an endogenous sponge of miR-30a-3p to decrease its activity, resulting in upregulation of ACT1(TRAF3IP2) expression, which in turn triggers TGF-β1/Smad3 signaling pathway activation, ultimately driving fibrotic progression after IVH. Collectively, our findings suggest that circHIPK3 and its coupling mechanism are implicated in IVH, providing compelling evidence that circHIPK3 could be a key therapeutic target against post-IVH communicating hydrocephalus.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2026.111751