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miR-29c-3p下调通过靶向BRD4加速脊髓损伤进展。

miR-29c-3p downregulation accelerates spinal cord injury progression by targeting BRD4.

作者信息

Wang Dawei, Wang Xiaona, Wu Yingshuang, Qi Sina, Hu Haifeng, Guo Jifei, Luo Yi

机构信息

Department of Orthopedics, Zhangjiakou First Hospital, No. 6 Libaisi Lane, Qiaoxi District, Zhangjiakou City, Hebei Province, 075000, China.

Department of Nurse, Zhangjiakou First Hospital, Zhangjiakou, Hebei, 075000, China.

出版信息

J Orthop Surg Res. 2025 Jul 25;20(1):703. doi: 10.1186/s13018-025-06108-0.

Abstract

BACKGROUND

Spinal cord injury (SCI) can cause severe motor and sensory deficits below the injury site. Studies have highlighted the multifaceted regulatory roles of miR-29c-3p in neuronal development and function; however, its role in SCI remains unclear.

METHODS

In this research 105 healthy controls and 159 patients with SCI were recruited. The miR-29c-3p and BRD4 levels in serum or cells were estimated by RT-qPCR. The diagnostic performance of miR-29c-3p was assessed by ROC curve. Moreover, cell viability and apoptosis were measured via CCK8 and flow cytometry. The pro-inflammatory cytokines were examined by ELISA assay. The pathological condition of SCI was modeled with LPS-induced PC12 cells. The target relationship between miR-29c-3p and BRD4 was verified by the dual-luciferase reporter assay.

RESULTS

Serum miR-29c-3p was remarkedly decreased in the SCI population and showed high clinical diagnostic performance. Under pathological conditions, the upregulation of miR-29c-3p effectively reversed the significant reduction in cell viability and the increase in apoptosis rate. Moreover, enhanced pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β were also attenuated by the upregulation of miR-29c-3p. BRD4 was identified as a target of miR-29c-3p and negatively regulated by miR-29c-3p.

CONCLUSIONS

A decrease in miR-29c-3p is a promising diagnostic indicator for SCI, and downregulation of miR-29c-3p accelerates the progression of SCI by targeting BRD4.

摘要

背景

脊髓损伤(SCI)可导致损伤部位以下出现严重的运动和感觉功能障碍。研究强调了miR-29c-3p在神经元发育和功能中的多方面调节作用;然而,其在SCI中的作用仍不清楚。

方法

本研究招募了105名健康对照者和159例SCI患者。通过RT-qPCR检测血清或细胞中的miR-29c-3p和BRD4水平。通过ROC曲线评估miR-29c-3p的诊断性能。此外,通过CCK8和流式细胞术检测细胞活力和凋亡情况。通过ELISA法检测促炎细胞因子。用脂多糖诱导的PC12细胞建立SCI的病理模型。通过双荧光素酶报告基因实验验证miR-29c-3p与BRD4之间的靶向关系。

结果

SCI患者血清miR-29c-3p明显降低,且具有较高的临床诊断性能。在病理条件下,miR-29c-3p的上调有效逆转了细胞活力的显著降低和凋亡率的增加。此外,miR-29c-3p的上调还减弱了包括TNF-α、IL-6和IL-1β在内的促炎细胞因子的表达。BRD4被确定为miR-29c-3p的靶标,并受到miR-29c-3p的负调控。

结论

miR-29c-3p的降低是SCI的一个有前景的诊断指标,miR-29c-3p的下调通过靶向BRD4加速SCI的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9144/12297646/0a6c367d58ad/13018_2025_6108_Fig4_HTML.jpg

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