Research Paper Volume 16, Issue 9 pp 8320—8335
Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis
- 1 Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China
- 2 Clinical Laboratory, Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China
- 3 Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China
Received: November 20, 2023 Accepted: March 26, 2024 Published: May 8, 2024
https://doi.org/10.18632/aging.205821How to Cite
Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Exosomal long non-coding RNAs (LncRNAs) play a crucial role in the pathogenesis of cerebrovascular diseases. However, the expression profiles and functional significance of exosomal LncRNAs in intracranial aneurysms (IAs) remain poorly understood. Through high-throughput sequencing, we identified 1303 differentially expressed LncRNAs in the plasma exosomes of patients with IAs and healthy controls. Quantitative real-time polymerase chain reaction (qRT-PCR) verification confirmed the differential expression of LncRNAs, the majority of which aligned with the sequencing results. ATP1A1-AS1 showed the most significant upregulation in the disease group. Importantly, subsequent in vitro experiments validated that ATP1A1-AS1 overexpression induced a phenotype switching in vascular smooth muscle cells, along with promoting apoptosis and upregulating MMP-9 expression, potentially contributing to IAs formation. Furthermore, expanded-sample validation affirmed the high diagnostic value of ATP1A1-AS1. These findings suggest that ATP1A1-AS1 is a potential therapeutic target for inhibiting IAs progression and serves as a valuable clinical diagnostic marker.
Abbreviations
LncRNA: long non-coding RNA; IA: intracranial aneurysm; SAH: subarachnoid haemorrhage; CTA: computed tomographic angiography; DSA: digital subtraction angiography; VSMC: vascular smooth muscle cell; NGS: next-generation sequencing; qRT-PCR: quantitative real-time polymerase chain reaction; WB: western blotting; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; NTA: nanoparticle tracking analysis; TEM: transmission electron microscopy; DE: differential expression; ATP1A1: Na/K-ATPase α1 gene; ATP1A1-AS1: Na/K-ATPase α1 gene antisense RNA 1; MMP: matrix metalloproteinase; MYH11: myosin heavy chain 11; CNN1: calponin 1; α-SMA: alpha-smooth muscle actin; ROC: operating characteristic; AUC: area under the curve.