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miRNA-9a-5p 通过破坏 ELAVL1/VEGF 轴缓解创伤性脑损伤。

microRNA-9a-5p disrupts the ELAVL1/VEGF axis to alleviate traumatic brain injury.

机构信息

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215000, PR China.

Department of Neonatology, Children's Hospital of Soochow University, Suzhou 215000, PR China.

出版信息

Exp Neurol. 2024 May;375:114721. doi: 10.1016/j.expneurol.2024.114721. Epub 2024 Feb 9.

Abstract

Plasma microRNA (miR)-9 has been identified as a promising diagnostic biomarker for traumatic brain injury (TBI). This study aims to investigate the possible role and mechanisms of miR-9a-5p affecting TBI. Microarray-based gene expression profiling of TBI was used for screening differentially expressed miRNAs and genes. TBI rat models were established. miR-9a-5p, ELAVL1 and VEGF expression in the brain tissue of TBI rats was detected. The relationship among miR-9a-5p, ELAVL1 and VEGF was tested. TBI modeled rats were injected with miR-9a-5p-, ELAVL1 or VEGF-related sequences to identify their effects on TBI. miR-9a-5p was poorly expressed in the brain tissue of rats with TBI. ELAVL1 was a downstream target gene of miR-9a-5p, which could negatively regulate its expression. Enforced miR-9a-5p expression prevented brain tissue damage in TBI rats by targeting ELAVL1. Meanwhile, ELAVL1 could increase the expression of VEGF, which was highly expressed in the brain tissue of rats with TBI. In addition, ectopically expressed miR-9a-5p alleviated brain tissue damage in TBI rats by downregulating the ELAVL1/VEGF axis. Overall, miR-9a-5p can potentially reduce brain tissue damage in TBI rats by targeting ELAVL1 and down-regulating VEGF expression.

摘要

血浆 microRNA(miR)-9 已被确定为外伤性脑损伤(TBI)有前途的诊断生物标志物。本研究旨在探讨 miR-9a-5p 影响 TBI 的可能作用和机制。采用基于微阵列的基因表达谱分析 TBI 筛选差异表达的 miRNA 和基因。建立 TBI 大鼠模型。检测 TBI 大鼠脑组织中 miR-9a-5p、ELAVL1 和 VEGF 的表达。检测 miR-9a-5p、ELAVL1 和 VEGF 之间的关系。向 TBI 模型大鼠注射 miR-9a-5p、ELAVL1 或 VEGF 相关序列,以确定它们对 TBI 的影响。miR-9a-5p 在 TBI 大鼠脑组织中表达水平较低。ELAVL1 是 miR-9a-5p 的下游靶基因,可负调控其表达。过表达 miR-9a-5p 通过靶向 ELAVL1 可防止 TBI 大鼠脑组织损伤。同时,ELAVL1 可增加 VEGF 的表达,VEGF 在 TBI 大鼠脑组织中高表达。此外,过表达 miR-9a-5p 通过下调 ELAVL1/VEGF 轴缓解 TBI 大鼠脑组织损伤。总之,miR-9a-5p 可能通过靶向 ELAVL1 并下调 VEGF 表达来减轻 TBI 大鼠的脑组织损伤。

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