医学分子生物学杂志2026,Vol.23Issue(5):492-501,10.
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
摘要
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.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Key words
lncRNA Vof16/heterogeneous nuclear ribonucleoprotein U/complexin-1/spinal cord injury/axonal growth分类
医药卫生引用本文复制引用
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):492-501,10.基金项目
湖南省自然科学基金(No.2023JJ50407) This work was supported by a grant from the Natural Science Foundation of Hunan Province(No.2023JJ50407). (No.2023JJ50407)