LncRNA Vof16通过HNRNPU/CPLX1影响脊髓损伤后轴突生长

doi:10.3870/j.issn.1672-8009.2026.05.003

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (5): 492-501.doi: 10.3870/j.issn.1672-8009.2026.05.003

LncRNA Vof16通过HNRNPU/CPLX1影响脊髓损伤后轴突生长

吴环宇¹, 雷凤婉², 李欢¹, 王坚³, 王炯¹, 彭涛³

湘南学院附属医院 ¹脊柱外科, ²消毒供应室, ³麻醉科湖南省郴州市, 423000

收稿日期:2025-12-12 出版日期:2026-09-30 发布日期:2026-09-30
通讯作者: 彭涛（E-mail：329362442@qq.com）
基金资助:
湖南省自然科学基金（No.2023JJ50407）

LncRNA Vof16 Promotes Post-SCI Axonal Growth via HNRNPU-Mediated Stabilization of CPLX1

WU Huanyu¹, LEI Fengwan², LI Huan¹, WANG Jian³, WANG Jiong¹, PENG Tao³

¹Department of Spinal Surgery, ²Disinfection Supply Room, ³Department of Anesthesiology, The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, 423000, China

Received:2025-12-12 Online:2026-09-30 Published:2026-09-30
Contact: PENG Tao （E-mail：329362442@qq.com ）
Supported by:
Natural Science Foundation of Hunan Province（No.2023JJ50407）

摘要/Abstract

摘要： 目的明确长链非编码RNA Vof16（lncRNA Vof16）是否通过异质性胞核核糖核蛋白U（heterogeneous nuclear ribonucleoprotein U, HNRNPU）/复合蛋白1（complexin 1, CPLX1）轴促进脊髓损伤（spinal cord injury, SCI）后轴突再生。方法动物水平实验中,将SD大鼠按随机数字表法分为Sham、SCI、SCI+sh-NC、SCI+Vof16-KD、SCI+oe-NC、SCI+Vof16-OE组。BBB评分及机械退缩阈值评估运动-感觉功能。RNA-seq联合qRT-PCR筛选并验证差异lncRNA。脊髓组织行qRT-PCR检测Vof16、HNRNPU、CPLX1表达。细胞实验中,分离原代脊髓神经元细胞进行氧糖剥夺（oxygen-glucose deprivation, OGD）,构建Vof16过表达（Vof16-OE）、HNRNPU过表达（HNRNPU-OE）或敲低（HNRNPU-KD）,及Vof16-OE+ HNRNPU-OE 和Vof16-OE+ HNRNPU-KD组。CCK-8、Transwell、免疫荧光分别检测细胞增殖、迁移及微管稳定性。验证Vof16-HNRNPU-CPLX1相互作用。结果 RNA-seq结果显示lncRNA Vof16在大鼠脊髓损伤后脊髓组织中高表达。过表达Vof16可提高OGD神经元增殖、迁移,增加ace-tubulin、降低tyr-tubulin（P<0.05）。机制上,Vof16直接结合HNRNPU,抑制其降解;HNRNPU进一步结合CPLX1 mRNA并增强其稳定性。HNRNPU敲低可逆转Vof16的促再生效应。体内实验显示,SCI+Vof16-OE组术后21 d BBB评分较SCI+oe-NC组提高（P<0.05）,机械退缩阈值降低,脊髓组织HNRNPU、CPLX1表达同步升高。结论 lncRNA Vof16能够招募HNRNPU,稳定CPLX1 mRNA,从而促进轴突再生。

关键词: lncRNA Vof16, 异质性胞核核糖核蛋白U, 复合蛋白1, 脊髓损伤, 轴突生长

Abstract: Objective To explore the effect of long non-coding RNA Vof16 （lncRNA Vof16） on axonal regeneration after spinal cord injury （SCI） via the heterogeneous nuclear ribonucleoprotein U （HNRNPU）/complexin-1 （CPLX1） axis. Methods In vivo, adult SD rats were randomly allocated to 6 groups： Sham group, SCI group, SCI+sh-NC group, SCI+Vof16-KD group, SCI+oe-NC group and SCI+Vof16-OE group. Motor and sensory functions were evaluated with BBB scores and mechanical withdrawal thresholds. Differentially expressed lncRNAs were screened by RNA-seq and validated by qRT-PCR; spinal-cord levels of Vof16, HNRNPU and CPLX1 were quantified by qRT-PCR. In vitro, primary spinal cord neurons were isolated for oxygen glucose deprivation （OGD）, Vof16 over-expression （Vof16-OE）, HNRNPU over-expression （HNRNPU-OE） or knock-down （HNRNPU-KD）, and Vof16-OE+ HNRNPU-OE and Vof16-OE+ HNRNPU-KD groups were constructed.Cell proliferation, migration and microtubule stability （Ace-tubulin/Tyr-tubulin） were assessed with CCK-8, Transwell assay and immunofluorescence, respectively. The Vof16-HNRNPU-CPLX1 interaction was verified by RNA pull-down, RIP and CLIP assays. Results RNAseq results showed that lncRNA Vof16 was highly expressed in spinal cord tissue after SCI in rats. Over-expressing Vof16 in OGD neurons increased proliferation and migration, raised ace-tubulin and reduced tyr-tubulin （P < 0.05）. Mechanistically, Vof16 directly bound HNRNPU and prevented its degradation; HNRNPU in turn bound CPLX1 mRNA and enhanced its stability. HNRNPU knock-down abolished the pro-regenerative effects of Vof16. In vivo, BBB scores at 21st day post-injury were higher and mechanical withdrawal thresholds were lower in the SCI+Vof16-OE group than in the SCI+oe-NC group （P < 0.05）, accompanied by elevated spinal-cord expression of HNRNPU and CPLX1. Conclusion lncRNA Vof16 recruits HNRNPU to stabilize CPLX1 mRNA, thereby promoting axonal regeneration after SCI.

Key words: lncRNA Vof16, heterogeneous nuclear ribonucleoprotein U, complexin -1, spinal cord injury, axonal growth

中图分类号:

R651.2

吴环宇, 雷凤婉, 李欢, 王坚, 王炯, 彭涛. LncRNA Vof16通过HNRNPU/CPLX1影响脊髓损伤后轴突生长[J]. 医学分子生物学杂志, 2026, 23(5): 492-501.

WU Huanyu, LEI Fengwan, LI Huan, WANG Jian, WANG Jiong, PENG Tao. LncRNA Vof16 Promotes Post-SCI Axonal Growth via HNRNPU-Mediated Stabilization of CPLX1[J]. Journal of Medical Molecular Biology, 2026, 23(5): 492-501.

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LncRNA Vof16通过HNRNPU/CPLX1影响脊髓损伤后轴突生长

LncRNA Vof16 Promotes Post-SCI Axonal Growth via HNRNPU-Mediated Stabilization of CPLX1

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