tRF-AspGTC Promotes Intracranial Aneurysm Formation by Controlling TRIM29-Mediated Galectin-3 Ubiquitination
Chao Wang,
Bing Yu,
Han Zhou,
Huanting Li,
Shifang Li,
Xiaolu Li,
Wentao Wang,
Yugong Feng,
Tao Yu
Affiliations
Chao Wang
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Bing Yu
Han Zhou
Department of Ophthalmology,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Huanting Li
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Shifang Li
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Xiaolu Li
Department of Critical Care Medicine,
Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, People’s Republic of China. 4Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Wentao Wang
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Yugong Feng
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
Tao Yu
Department of Neurosurgery and Institute for Translational Medicine,
The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China.
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.
