LncRNA TUG1 Repressed Angiogenesis by Promoting the Ubiquitination of HuR and Inhibiting Its Nuclear Translocation in Cerebral Ischemic Reperfusion Injury.

IF 14.3 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Science Pub Date : 2025-01-31 DOI:10.1002/advs.202413333

Hongxiang Jiang, Qiang Cai, Peidong He, Fei Li, Qianxue Chen

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引用次数: 0

Abstract

Although both Taurine Upregulated Gene 1(TUG1) and Human Antigen R (HuR) play significant regulatory roles in Cerebral Ischemic Reperfusion Injury (CIRI), their potential pro-angiogenesis mechanisms in CIRI remain unclear.

Methods: Herein, the biological roles of TUG1 and HuR in angiogenesis are first confirmed. Following that, HuR-binding VEGFA mRNAs are identified via the Fluorescence In Situ Hybridization (FISH), RNA Immunoprecipitation (RIP), and Cross-Linking Immunoprecipitation (CLIP) assays. Actinomycin D and polysomal assays are also employed to confirm VEGFA mRNA stability. The co-localization of TUG1 with HuR is confirmed using FISH, while the RIP and RNA pull-down assays are employed to elucidate their interplay. The direct binding between TUG1 and HuR is confirmed through the CLIP assay. Co-Immunoprecipitation (Co-IP) and rescue experiments are performed to further elucidate TUG1-HuR interactions.

Results: While TUG1 repressed angiogenesis and aggravated CIRI, HuR exerted contrary effects. Specifically, HuR bound directly to VEGFA mRNA, a phenomenon that enhanced VEGFA mRNA stability. Conversely, TUG1 binds to HuR directly, inhibiting its nuclear translocation and promoting its ubiquitination, ultimately reducing VEGFA mRNA stability.

Conclusions: It is found that TUG1 can inhibit angiogenesis in CIRI through the HuR/VEGFA mRNA axis.

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来源期刊

Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY

CiteScore

18.90

自引率

2.60%

发文量

1602

审稿时长

1.9 months

期刊介绍： Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.