Wang Chao, Yu Bing, Zhou Han, Li Huanting, Li Shifang, Li Xiaolu, Wang Wentao, Feng Yugong, Yu Tao
Department of Neurosurgery and Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China.
Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China.
Research (Wash D C). 2025 Jan 7;8:0574. doi: 10.34133/research.0574. eCollection 2025.
Transfer RNA-derived small RNAs, a recently identified class of small noncoding RNAs, play a crucial role in regulating gene expression and are implicated in cerebrovascular diseases. However, the specific biological roles and mechanisms of transfer RNA-derived small RNAs in intracranial aneurysms (IAs) remain unclear. In this study, we identified that the transfer RNA-Asp-GTC derived fragment (tRF-AspGTC) is highly expressed in the IA tissues of both humans and mice. tRF-AspGTC promotes IA formation by facilitating the phenotypic switching of vascular smooth muscle cells, increasing of matrix metalloproteinase 9 expression, and inducing of oxidative stress and inflammatory responses. Mechanistically, tRF-AspGTC binds to galectin-3, inhibiting tripartite motif 29-mediated ubiquitination and stabilizing galectin-3. This stabilization activates the toll-like receptor 4/MyD88/nuclear factor kappa B pathway, further driving phenotypic switching and inflammation. Clinically, circulating exosomal tRF-AspGTC demonstrates strong diagnostic efficacy for IAs and is identified as an independent risk factor for IA occurrence. These findings highlight the potential of tRF-AspGTC as a promising diagnostic biomarker and therapeutic target for IAs.
转运RNA衍生的小RNA是最近发现的一类小非编码RNA，在调节基因表达中起关键作用，并与脑血管疾病有关。然而，转运RNA衍生的小RNA在颅内动脉瘤（IA）中的具体生物学作用和机制仍不清楚。在本研究中，我们发现转运RNA-Asp-GTC衍生片段（tRF-AspGTC）在人和小鼠的IA组织中高度表达。tRF-AspGTC通过促进血管平滑肌细胞的表型转换、增加基质金属蛋白酶9的表达以及诱导氧化应激和炎症反应来促进IA形成。机制上，tRF-AspGTC与半乳糖凝集素-3结合，抑制三重基序29介导的泛素化并稳定半乳糖凝集素-3。这种稳定激活了Toll样受体4/髓样分化因子88/核因子κB通路，进一步推动表型转换和炎症。临床上，循环外泌体tRF-AspGTC对IA具有很强的诊断效力，并被确定为IA发生的独立危险因素。这些发现突出了tRF-AspGTC作为IA有前景的诊断生物标志物和治疗靶点的潜力。
