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 role...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.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82370425 and 81870914)the Taishan Scholar Program of Shandong Province(No.tsqn202408156).
文摘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.
