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

doi:10.3870/j.issn.1672-8009.2026.05.003

Journal of Medical Molecular Biology ›› 2026, Vol. 23 ›› Issue (5): 492-501.doi: 10.3870/j.issn.1672-8009.2026.05.003

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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）

Abstract

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

CLC Number:

R651.2

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.

References

[1] LU Y,SHANG Z,ZHANG W,et al.Global incidence and characteristics of spinal cord injury since 2000-2021: a systematic review and meta-analysis[J]. BMC Med,2024,22(1):285.
[2] ZELLER S L,STEIN A,FRID I,et al.Critical care of spinal cord injury[J]. Curr Neurol Neurosci Rep,2024,24(9):355-363.
[3] NEKANTI U,SAKTHIVEL P,ZAHEDI A,et al. Multichannel bridges and NSC synergize to enhance axon regeneration,myelination,synaptic reconnection,and recovery after SCI[J]. Res Sq,2023:rs.3.rs-rs.3044426.
[4] FILOUS A R,SCHWAB J M.Determinants of axon growth,plasticity,and regeneration in the context of spinal cord injury[J]. Am J Pathol,2018,188(1):53-62.
[5] DING L,FU W J,DI H Y,et al.Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis[J]. Neural Regen Res,2020,15(8):1560-1567.
[6] HU Y,SUN Y F,YUAN H,et al.Vof16-miR-185-5p-GAP43 network improves the outcomes following spinal cord injury via enhancing self-repair and promoting axonal growth[J]. CNS Neurosci Ther,2024,30(4):e14535.
[7] WANG Y C,FENG G Y,XIA Q J,et al.Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats[J]. Apoptosis,2016,21(4):404-420.
[8] 胡振鑫,刘娅妮,叶蓁,等. 京尼平苷酸通过稳定微管促进脊髓损伤后轴突生长[J]. 中国生物化学与分子生物学报,2019,35(5):551-558.
HU Z X,LIU Y N,YE Z,et al.Geniposidic acid enhances axonal regeneration after spinal cord injury by stablilizing microtubule[J]. Chin J Biochem Mol Biol,2019,35(5):551-558.
[9] HÅKANSSON S,TUCI M,BOLLIGER M,et al. Data-driven prediction of spinal cord injury recovery: An exploration of current status and future perspectives[J]. Exp Neurol,2024,380:114913.
[10] QUAN Z,ZHENG D,QING H.Regulatory roles of long non-coding RNAs in the central nervous system and associated neurodegenerative diseases[J]. Front Cell Neurosci,2017,11:175.
[11] LI P,JIA Y,TANG W,et al.Roles of non-coding RNAs in central nervous system axon regeneration[J]. Front Neurosci,2021,15:630633.
[12] ZHANG X M,ZENG L N,YANG W Y,et al.Inhibition of LncRNA Vof-16 expression promotes nerve regeneration and functional recovery after spinal cord injury[J]. Neural Regen Res,2022,17(1):217-227.
[13] LIN G,LIN H,ZHUO R,et al.GCN5/KAT2A contributes to axon growth and neurogenesis[J]. Neurosci Lett,2022,784:136742.
[14] CAI X,XIE Z,ZHAO J,et al.FGF20 promotes spinal cord injury repair by inhibiting the formation of necrotic corpuscle P-MLKL/P-RIP1/P-RIP3 in neurons[J]. J Cell Mol Med,2024,28(24):e70109.
[15] SAPIR T,KSHIRSAGAR A,GORELIK A,et al.Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex[J]. Nat Commun,2022,13(1):4209.
[16] QUAN L,UYEDA A,MANABE I,et al.Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury[J]. J Neuroinflammation,2025,22(1):28.
[17] SALEHI S,ZARE A,PREZZA G,et al.Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr[J]. Nat Commun,2023,14(1):4158.
[18] FUKUDA N,FUKUDA T,PERCIPALLE P,et al.Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons[J]. Cell Rep,2023,42(5):112398.
[19] SHI M,XU H,HU R,et al.Identification and validation of synapse-related hub genes after spinal cord injury by bioinformatics analysis[J]. Comb Chem High Throughput Screen,2024,27(4):599-610.
[20] LÓPEZ-MURCIA F J,LIN K H,BERNS M M M,et al. Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion[J]. Proc Natl Acad Sci U S A,2024,121(15):e2320505121.

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

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