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Background: Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence‐associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor‐derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation‐induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear. Methods: Beta‐galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence‐associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation‐induced sEVs. Liquid chromatography–tandem mass spectrometry (LC–MS) was used to explore changes in the levels of proteins in radiation‐induced sEVs. Cell Counting Kit‐8 and colony formation assays were performed to investigate the function of radiation‐induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation‐induced sEVs and V‐9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence. Results: We determined that the radiation‐induced SASP triggered OSCC cell proliferation. Additionally, radiation‐induced sEVs exacerbated OSCC cell malignancy. LC–MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation‐induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation‐induced sEVs in OSCC. Conclusion: Radiation‐induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients. [ABSTRACT FROM AUTHOR]

Collapse of the microvascular system is a prerequisite for radiation‐induced bone loss. Since type H vessels, a specific bone vessel subtype surrounded by platelet‐derived growth factor receptor β+ (PDGFRβ+) perivascular cells (PVCs), has been recently identified to couple angiogenesis and osteogenesis, we hypothesize that type H vessel injury initiates PDGFRβ+ PVC dysfunction, which contributes to the abnormal angiogenesis and osteogenesis after irradiation. In this study, we found that radiation led to the decrease of both type H endothelial cell (EC) and PDGFRβ+ PVC numbers. Remarkably, results from lineage tracing showed that PDGFRβ+ PVCs detached from microvessels and converted the lineage commitment from osteoblasts to adipocytes, leading to vascular injury and bone loss after irradiation. These phenotype transitions above were further verified to be associated with the decrease in hypoxia‐inducible factor‐1α (HIF‐1α)/PDGF‐BB/PDGFRβ signalling between type H ECs and PDGFRβ+ PVCs. Pharmacological blockade of HIF‐1α/PDGF‐BB/PDGFRβ signalling induced a phenotype similar to radiation‐induced bone damage, while the rescue of this signalling significantly alleviated radiation‐induced bone injury. Our findings show that the decrease in HIF‐1α/PDGF‐BB/PDGFRβ signalling between type H ECs and PDGFRβ+ PVCs after irradiation affects the homeostasis of EC‐PVC coupling and plays a part in vascular damage and bone loss, which has broad implications for effective translational therapies. [ABSTRACT FROM AUTHOR]

The peroxidase family of peroxiredoxins (PRDXs) plays a vital role in maintaining the intracellular balance of ROS. However, their function in head and neck squamous cell carcinoma (HNSCC) has not been investigated. We therefore explored the value of PRDXs in HNSCC. We found that the expression of PRDX1, PRDX4, and PRDX5 in HNSCC increased while the expression of PRDX2 decreased. Moreover, the high expression of PRDX4/5/6 indicated a poor prognosis. Lower expression of PRDX1/5 was linked to more immune cell infiltration, higher expression of immune-related molecules and a more likely response to anti-PD-1 treatment. Moreover, PRDX5 knockdown inhibited HNSCC cell proliferation, invasion and metastasis and it might promote apoptosis through its antioxidant property. Taken together, our study highlights the potential role of PRDXs in HNSCC. The function of PRDX5 in the development of HNSCC and the formation of the immune microenvironment makes it a promising potential therapeutic target. [ABSTRACT FROM AUTHOR]

TP53INP2 plays an important role in regulating gene transcription and starvation-induced autophagy, however, its function in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we assessed the expression and prognostic value of TP53INP2. In addition, RNAseq, miRNAseq, copy number variation, and mutation profiles from The Cancer Genome Atlas (TCGA) dataset were applied to evaluate the distinctive genomic patterns related to TP53INP2 expression. We found that TP53INP2 expression was lower in HNSCC compared with normal controls. Patients with higher TP53INP2 expression had longer survival time. Knockdown of TP53INP2 promoted cell viability. Functional analysis exhibited that TP53INP2 was linked to DNA replication, DNA repair, cell cycle, and multiple metabolic pathways. Moreover, TP53INP2 might affect the expression of multiple genes via enhancing the transcriptional activity of nuclear hormone receptors. A competing endogenous RNA (ceRNA) network consisting of 33 lncRNAs, eight miRNAs, and 13 mRNAs was constructed based on the expression of TP53INP2. Taken together, our study highlights the potential value of TP53INP2 in predicting the survival of HNSCC and its important role in the genesis and development of HNSCC. [ABSTRACT FROM AUTHOR]

Background: Alternative splicing (AS) plays an essential role in tumorigenesis and progression. This study aimed to develop a novel prognostic model based on the AS events to obtain more accurate survival prediction and search for potential therapeutic targets in oral squamous cell carcinoma (OSCC). Methods: Seven types of AS events in 326 OSCC patients with RNA-seq were obtained from the TCGA SpliceSeq tool and the TCGA database. Cox analysis, the least absolute shrinkage and selection operator Cox regression and random forest were employed to establish prognostic models. Genomics of Drug Sensitivity in Cancer (GDSC) was adopted to estimate the possible drug sensiticity. Prognostic splicing factor (SF)-AS network was constructed by Cytoscape. Results: The final model included 12 AS events, showing satisfactory performance. The area under the curve for 3- and 5-year survival in the training cohort was 0.83 and 0.82, respectively while that in internal validation was 0.83 and 0.82 accordingly. The calibration curve also indicated a satisfactory agreement between the observation and the predictive values. Low-risk patients stratified by the final model presented higher sensitivity to three chemo drugs. Besides, the prognostic SF-AS regulatory network contained five key SFs and 62 AS events. Conclusions: We developed a powerful prognostic AS signature for OSCC and deepened the understanding of SF-AS network regulatory mechanisms. Low-risk patients tended to be more sensitive to the three chemo drugs while five key SFs including CELF2, TIA1, HNRNPC, HNRNPK, and SRSF9 were identified as potential prognostic biomarkers, which may offer new prospects for effective therapies of OSCC. [ABSTRACT FROM AUTHOR]

The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both in vitro and in vivo, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment. [ABSTRACT FROM AUTHOR]

Collapse of the microvascular system is a prerequisite for radiation-induced bone loss. Since type H vessels, a specific bone vessel subtype surrounded by platelet-derived growth factor receptor β + (PDGFRβ + ) perivascular cells (PVCs), has been recently identified to couple angiogenesis and osteogenesis, we hypothesize that type H vessel injury initiates PDGFRβ + PVC dysfunction, which contributes to the abnormal angiogenesis and osteogenesis after irradiation. In this study, we found that radiation led to the decrease of both type H endothelial cell (EC) and PDGFRβ + PVC numbers. Remarkably, results from lineage tracing showed that PDGFRβ + PVCs detached from microvessels and converted the lineage commitment from osteoblasts to adipocytes, leading to vascular injury and bone loss after irradiation. These phenotype transitions above were further verified to be associated with the decrease in hypoxia-inducible factor-1α (HIF-1α)/PDGF-BB/PDGFRβ signalling between type H ECs and PDGFRβ + PVCs. Pharmacological blockade of HIF-1α/PDGF-BB/PDGFRβ signalling induced a phenotype similar to radiation-induced bone damage, while the rescue of this signalling significantly alleviated radiation-induced bone injury. Our findings show that the decrease in HIF-1α/PDGF-BB/PDGFRβ signalling between type H ECs and PDGFRβ + PVCs after irradiation affects the homeostasis of EC-PVC coupling and plays a part in vascular damage and bone loss, which has broad implications for effective translational therapies., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Backgrounds: Immunotherapy is effective in a subset of head and neck squamous cell carcinoma (HNSCC). However, the unfavorable response rate and inadequate biomarkers for stratifying patients have primarily limited its clinical application. Considering transcriptional factors (TFs) play essential roles in regulating immune activity during HNSCC progression, we comprehensively analyzed the expression alterations of TFs and their prognostic values., Methods: Gene expression datasets and clinical information of HNSCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository. Then, Brain abundant membrane attached signal protein 1 (BASP1) was screened out of differentially expressed TFs by univariate and multivariate survival analysis. Tumor immune dysfunction and exclusion (TIDE) was applied to analyze the response to immunotherapy of BASP1 high/low patients. Meanwhile, GO, KEGG and GSEA analyses were used to enrich the pathways between the BASP1 high and BASP1 low groups. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, EPIC and quanTiseq algorithms were applied to explore immune infiltrations. Also, immune cycle analysis was conducted by ssGSEA. Additionally, lipid peroxidation, glutathione and reactive oxygen species were performed to detect the ferroptosis alternations., Results: BASP1 was upregulated and associated with poor survival in HNSCC patients. BASP1 high patients exhibited better response rates to anti-PD-1 immunotherapy and higher expressions of immune checkpoint inhibitors. GO, KEGG and GSEA analyses indicated that the expression of BASP1 was related to several immune-related pathways and immunogenic ferroptosis signature. The infiltration of activated CD8 + T cells was authenticated to be decreased in BASP1 high patients. Furthermore, BASP1 was identified to be positively correlated with T cell dysfunction and immune escape. Moreover, silencing BASP1 triggered ferroptosis in HNSCC cells, representing as increased LDH, lipid peroxidation and ROS levels, and reduced glutathione synthesis., Conclusions: We demonstrated that BASP1 suppressed immunogenic ferroptosis to induce immunosuppressive tumor microenvironment. BASP1 plays a critical role in immune response, and might be a promising classifier for selecting HNSCC patients who benefit from current immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Xu, Wang, Zhang, Chen, Yang, Chen, Cheng, Xia and Ren.)

Glycolysis markers including glucose transporter 1 (GLUT1), monocarboxylate transporter 4 (MCT4), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) play vital roles in head and neck squamous cell carcinoma (HNSCC). However, their prognostic value in HNSCC is still controversial. In this meta-analysis, we searched the PubMed, Web of Science and Cochrane Library databases and included thirty-seven studies (3272 patients) that met the inclusion criteria. Higher expression levels of the glycolysis markers in tumor tissues correlated with poorer overall survival (OS; P < 0.001), disease-free survival (DFS; P = 0.03) and recurrence-free survival (RFS; P < 0.001) of HNSCC patients. Subgroup and sensitivity analyses demonstrated that higher expression levels of GLUT1 ( P < 0.001), MCT4 ( P = 0.002), HK2 ( P = 0.002) and PKM2 ( P < 0.001) correlated with poorer OS among HNSCC patients. Higher expression of MCT4 ( P < 0.001) and PKM2 ( P = 0.008) predicted poorer DFS among HNSCC patients. However, GLUT4 expression levels did not associate with clinical outcomes in HNSCC patients. These results demonstrate that glycolysis markers, such as GLUT1, MCT4, HK2 and PKM2, are potential prognostic predictors and therapeutic targets in HNSCC.

Background : We previously demonstrated that Proline rich 11 ( PRR11 ) gene is associated with the development and progression of tongue squamous cell carcinoma (TSCC), but the underlying mechanism is unknown. This study aimed to investigate the molecular mechanism underlying oncogenic potential of PRR11 in TSCC cells. Methods : Overexpression and knockdown of PRR11 were performed by plasmid transfection into SCC15 and HSC3 human TSCC cells. Expressions of mRNA and protein were assessed by qRT-PCR and Western blot, respectively. Cell proliferation and invasion were determined by CCK-8 and Transwell assay, respectively. In vivo tumor growth and cell cycle were determined by a nude mice model of subcutaneous tumorigenesis and flow cytometry, respectively. Results : Overexpression of PRR11 significantly enhanced TSCC cells proliferation and the invasive ability of TSCC cells, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. In addition, the in vivo subcutaneous tumorigenicity assay showed that PRR11 knockdown significantly reduced tumor size and the Ki67 (a proliferation marker)expression in the tumor tissue. Flow cytometry analysis revealed that PRR11 overexpression significantly decreased the proportion of cells in S phase, whereas PRR11 knockdown in TSCC cells exhibited a reverse trend. Furthermore, PRR11 overexpression simultaneously down-regulated two cyclin-dependent kinase inhibitors (CKIs), p21 and p27 and up-regulated CDK2 and Cyclin A2 in TSCC cells. PRR11 knockdown again exhibited reverse trends of expressions of the above proteins. Conclusion : These results suggested that PRR11 promoted cell proliferation by regulating the expressions of p21, p27, CDK2 and Cyclin A to facilitate S/G phase transition in TSCC cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Elucidation of the mechanisms of T-cell-mediated antitumor responses will provide information for the rational design and development of cancer immunotherapies. Here, we found that calnexin, an endoplasmic reticulum (ER) chaperone protein, is significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells is associated with inhibited T-cell infiltration in tumor tissues and correlates with poor survival of patients with OSCC. We found that calnexin inhibits the proliferation of CD4 + and CD8 + T cells isolated from the whole blood of healthy donors and patients with OSCC and inhibits the secretion of IFNγ, TNFα, and IL2 from these cells. Furthermore, in a melanoma model, knockdown of calnexin enhanced the infiltration and effector functions of T cells in the tumor microenvironment and conferred better control of tumor growth, whereas treatment with a recombinant calnexin protein impaired the infiltration and effector functions of T cells and promoted tumor growth. We also found that calnexin enhanced the expression of PD-1 on CD4 + and CD8 + T cells by restraining the DNA methylation status of a CpG island in the PD-1 promoter. Thus, this work uncovers a mechanism by which T-cell antitumor responses are regulated by calnexin in tumor cells and suggests that calnexin might serve as a potential target for the improvement of antitumor immunotherapy., (©2018 American Association for Cancer Research.)

Oral squamous cell carcinoma (OSCC) is a common and aggressively malignant tumor of the head and neck region. Long non-coding RNAs (lncRNAs) are important regulatory molecules in many types of cancer. However, there are limited studies on the role of lncRNAs in OSCC. In this study, we identified that lncRNA P4713 was one of the most up-regulated lncRNAs in OSCC by exploring the expression profile of lncRNAs/mRNAs in four pairs of OSCC samples and adjacent non-cancer tissues. In addition, silencing of P4713 inhibited OSCC proliferation, migration, and invasion in vitro . Furthermore, through bioinformatics analysis and functional experiments, we found that decreased P4713 expression affected the expression and phosphorylation of Janus Kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3. Taken together, the results suggest that P4713 contributes to OSCC cell proliferation, migration, and invasion by activating the JAK/STAT3 pathway. Accordingly, this molecule could be a potential biomarker and therapeutic target in the treatment of OSCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Increasing evidence has demonstrated a significant role for long non-coding RNAs (lncRNAs) in tumorigenesis. However, their functions in nasopharyngeal carcinoma (NPC) metastasis remain largely unknown. In this study, a model comparing high and low metastatic NPC cell lines (5-8F vs. 6-10B and S18 vs. S26) was constructed to determine the expression profile of lncRNAs using the microarray analysis, and we found 167 lncRNAs and 209 mRNAs were differentially expressed. Bioinformatic analysis indicated that the dysregulated mRNAs participated in important biological regulatory functions in NPC. Validation of 26 significantly dysregulated lncRNAs by qRT-PCR showed the expression patterns of 22 lncRNAs were in accordance with the microarray data. Furthermore, the expression level of ENST00000470135, which was the most upregulated lncRNA in high metastatic cell lines, was significantly higher in NPC cell lines and tissues with lymph node metastasis (LNM) and knocking down ENST00000470135 suppressed the migration, invasion and proliferation of NPC cells in vitro. In conclusion, our study revealed expression patterns of lncRNAs in NPC metastasis. The dysregulated lncRNAs may act as novel biomarkers and therapeutic targets for NPC., Competing Interests: The authors declare no conflicts of interest. The funders which supported the work had no role in the study design, data collection, analysis, decision to publish or the preparation of the manuscript.

Dysregulation of miRNAs has been shown to contribute to the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Our previous microarray data showed that miR-16 expression is significantly decreased in archived NPC tissues. Here, we confirmed that miR-16 was reduced in NPC cell lines and freshly-frozen samples. Ectopic expression of miR-16 suppressed NPC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and metastatic colonization in the lung in vivo. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a direct target of miR-16, and both phosphoinositide-3- kinase/AKT (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways were repressed after miR-16 overexpression. In addition, the restoration of FGF2 reversed the suppressive effects of miR-16. Together, these results indicated that miR-16 suppresses NPC carcinogenesis and progression by targeting FGF2, thereby representing a potential target for miRNA-based therapy for NPC in the future.

This study assessed the incidence and prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally advanced NPC were subjected to immunohistochemistry to analyze MET protein expression and fluorescence in situ hybridization to assess MET amplification status. In total, 139/376 (37.0%) patients had MET protein overexpression; of whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006) and death (P < 0.001); MET amplification was significantly associated with death (P = 0.021). A positive correlation was observed between MET copy number status and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis demonstrated MET overexpression was an independent prognostic factor for overall survival (OS; HR, 1.99; 95% CI, 1.38-2.87; P < 0.001) and disease-free survival (DFS; HR, 1.85; 95% CI, 1.33-2.57; P < 0.001), and MET amplification was independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001) and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial.

Background: The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector., Methods: A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino)-1-propylamine (DMAPA-Glyp) and 1-(2-aminoethyl) piperazine (AEPZ-Glyp) residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid-base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA) condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney) and the CNE2 (human nasopharyngeal carcinoma) cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley rats) was evaluated to identify the safety and transfection efficiency., Results: The hyperbranched cationic glycogen derivatives conjugated with DMAPA and AEPZ residues were synthesized. They exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI). They were able to bind and condense pDNA to form the complexes of 100-250 nm in size. The transfection efficiency of the DMAPA-Glyp/pDNA complexes was higher than those of the AEPZ-Glyp/pDNA complexes in both the 293T and CNE2 cells, and almost equal to those of bPEI. Furthermore, pDNA could be more safely delivered to the blood vessels in brain tissue of Sprague Dawley rats by the DMAPA-Glyp derivatives, and then expressed as green fluorescence protein, compared with the control group., Conclusion: The hyperbranched cationic glycogen derivatives, especially the DMAPA-Glyp derivatives, showed high gene-transfection efficiency, good blood compatibility, and low cyto toxicity when transfected in vitro and in vivo, which are novel potential nonviral gene vectors.

Study Design: We used a complete spinal cord transection model and locomotor function, histological, and immunohistochemical examinations to evaluate the effects of local injection of lentivirus/LINGO-1-short hairpin RNA (VL) on rats with spinal cord injury (SCI)., Objective: To demonstrate the neuroregenerative and neuroprotective effects of LINGO-1 RNAi on complete transection SCI rats., Summary of Background Data: LINGO-1 has been reported as a negative regulator of axonal sprouting and its antagonist was determined to improve functional outcomes in SCI rats. However, it has not been assessed whether blockade of LINGO-1 mediated by lentivirus vectors could stimulate neural recovery after SCI., Methods: Complete spinal cord transection was made at T10 level. Suspension of lentivirus vectors encoding LINGO-1-short hairpin RNA was injected into the lesion gap. Controls received control vectors in the same manner and the sham group was subjected to laminectomy only. The Basso-Beattie-Bresnahan scale and surface righting reflex test were used to evaluate functional outcomes. Finally, the spinal cords were harvested for histological and immunohistochemical analysis., Results: The treatment with VL improved Basso-Beattie-Bresnahan scores and surface righting reflex after SCI. Tissue repair was facilitated and the cavity area was significantly decreased in VL-treated animals. More sprouting and myelinated nerve fibers were detected within the injured site in the VL group as compared with the control. In addition, the number of survival neurons and oligodendrocytes around the epicenter was notably higher under the VL condition., Conclusion: Local injection of lentivirus/LINGO-1-short hairpin RNA after complete transection of spinal cord resulted in meaningful histological and functional outcomes in rats. The mechanism of VL protection may be related to its promotion of axonal sprouting, remyelination, and cell survival.