Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

Liu, Xia; Liu, Shousheng; Fu, Juan; Huang, Jinsheng; Weng, Chengyin; Fang, Xisheng; Guan, Mingyu; Wu, Yong; Yang, Lin; Liu, Guolong

doi:10.3892/ol.2019.10797

Cited by 5 publications

(7 citation statements)

References 35 publications

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“…However, the function and mechanism of NSE in SCLC were still unclear. Our previous research found that silencing NSE could inhibit the proliferation and migration of SCLC cells (13). Our clinical data also indicated that high levels of serum NSE were positively correlated with tumor metastasis in SCLC patients.…”

Section: Discussionsupporting

confidence: 66%

“…However, the effect and molecular mechanism of NSE in promoting distant metastasis of SCLC are still unclear. In addition, our previous research also found that knocking down NSE can inhibit the proliferation and migration of SCLC cells (13). Therefore, we would like to further study whether NSE can promote SCLC cell migration, invasion and distant metastasis, and to clarify its molecular mechanisms.…”

Section: Introductionmentioning

confidence: 92%

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Neuron Specific Enolase Promotes Metastasis by Activating the Wnt/β-catenin Pathway in Small Cell Lung Cancer

Zha

Zhang

et al. 2020

Preprint

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BackgroundNeuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. MethodsWe conducted an investigation in SCLC patients and then analyzed the association between NSE concentration and the distant metastasis. The migration and invasion were analyzed using Wound-healing and Transwell assays. The proteins and mRNA levels were measured by western blot and qRT-PCR. Furthermore, we conducted Gene Set Enrichment Analysis (GSEA) to explore potential signaling pathways. The interaction between NSE and β-catenin was verified through CO-IP experiments. In addition, animal experiments were performed in tumor metastasis models of nude mice.ResultIn this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration, invasion and metastasis of SCLC cells, while knocking down NSE inhibited these effects. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells, while knocking down NSE inhibited this effect. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and tumor distant metastasis of SCLC cells by activating Wnt/β-catenin pathway in vivo.ConclusionOur results revealed that NSE could promote EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 92%

Neuron Specific Enolase Promotes Metastasis by Activating the Wnt/β-catenin Pathway in Small Cell Lung Cancer

Zha

Zhang

et al. 2020

Preprint

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“…Liu's team silenced NSE in SCLC cell lines using a loss-of-function approach and found that the knockdown of NSE suppressed proliferation, colony formation, and migration of SCLC cells, compared to those of the control group. Also, the silencing of NSE led to the downregulation of metastasis promoter gene vascular endothelial growth factor (VEGF) and upregulation of metastasis suppressor genes NM23 and E-cadherin [44]. These experimental results may support that the elevated NSE of SCLC patients is associated with unfavorable outcome.…”

Section: Discussionmentioning

confidence: 71%

Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis

et al. 2020

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Background: Neuron-specific enolase (NSE) has become a widely used and easily attainable laboratory assay of small cell lung cancer (SCLC). However, the prognostic value of NSE for SCLC patients remains controversial. The aim of the study was to evaluate the correlation between elevated serum NSE before therapy and survival of SCLC patients. Methods: We performed a systematic review and meta-analysis. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register from the inception dates to December 2019. Eligible articles were included according to inclusion and exclusion criteria; then, data extraction and quality assessment were performed. The primary outcome was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Results: We identified 18 studies comprising 2981 patients. Pooled results revealed that elevated NSE was associated with worse OS (HR = 1.78, 95% CI 1.55-2.06, p < 0.001) and PFS (HR = 1.50, 95% CI 1.16-1.93, p = 0.002). In subgroup analysis, elevated NSE did not predict worse OS in patients who received only chemotherapy (HR 1.22, 95% CI 0.96-1.55, p = 0.10) or part of whom received surgical resection before chemotherapy and radiotherapy (HR = 2.16, 95% CI 0.82-5.69, p = 0.12). Conclusion: Elevated serum NSE before any therapy of SCLC patients may be a negative prognostic factor for OS and PFS. The prognostic value of NSE for OS was particularly observed in patients treated by standard management.

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“…Measurement of plasma NSE levels has been used as a biomarker for various applications (Isgro et al, 2015). For example, it is a useful indicator of neural maturation, and is currently the most widely used biomarker for small cell lung cancer (SCLC), and it has been shown to have a direct effect in cell growth and migration in vitro on different SCLC cell lines (Zhou et al, 2011;Liu et al, 2019). Additionally, it is also used in the diagnosis and prognosis of other type of cancers as the non-small cell lung cancer (NSCLC), neuroendocrine tumors (NETs), neuroblastoma, brain cancer and brain injury (TBI) (Isgrò et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Peptides of neuron specific enolase as potential ASD biomarkers: From discovery to epitope mapping

Ramirez-Celis

Edmiston

Schauer

et al. 2020

Brain, Behavior, and Immunity

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Autism spectrum disorder (ASD) is an important health issue and affects 1 in 59 children in the US. Prior studies determined that maternal autoantibody related (MAR) autism is thought to be associated with ~23% of ASD cases. We previously identified seven MAR-specific autoantigens including CRMP1, CRMP2, GDA, LDHA, LDHB, STIP1, and YBX1. We subsequently described the epitope peptide sequences recognized by maternal autoantibodies for each of the seven ASDspecific autoantigens. The aim of the current study was to expand upon our previous work and identify additional antigens recognized by the ASD-specific maternal autoantibodies, as well as to map the unique ASD-specific epitopes using microarray technology. Fetal Rhesus macaque brain tissues were separated by molecular weight and a fraction containing bands between 37 and 45 kDa was analyzed using 2-D gel electrophoresis, followed by peptide mass mapping using MALDI-TOF MS and TOF/TOF tandem MS/MS. Using this methodology, Neuron specific enolase (NSE) was identified as a target autoantigen and selected for epitope mapping. The full NSE sequence was translated into 15-mer peptides with an overlap of 14 amino acids onto microarray slides and probed with maternal plasma from mothers with an ASD child and from mothers with a Typically Developing child (TD) (ASD = 27 and TD = 21). The resulting data were analyzed by T-test. We found 16 ASD-specific NSE-peptide sequences for which four sequences were statistically significant (p < 0.05) using both the t-test and SAM t-test: DVAASEFYRDGKYDL (p = 0.047; SAM score 1.49), IEDPFDQDDWAAWSK (p = 0.049; SAM score 1.49), ERLAKYNQLMRIEEE (p = 0.045; SAM score 1.57), and RLAKYNQLMRIEEEL (p = 0.017; SAM score 1.82). We further identified 5 sequences that were recognized by both ASD and TD antibodies suggesting a large immunodominant epitope (DYPVVSIEDPFDQDDWAAW). While maternal autoantibodies against the NSE protein are present both in mothers with ASD and mothers of TD children, there are several ASD-specific epitopes that can potentially be used as *

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Knockdown of neuron‑specific enolase suppresses the proliferation and migration of NCI‑H209 cells

Cited by 5 publications

References 35 publications

Neuron Specific Enolase Promotes Metastasis by Activating the Wnt/β-catenin Pathway in Small Cell Lung Cancer

Neuron Specific Enolase Promotes Metastasis by Activating the Wnt/β-catenin Pathway in Small Cell Lung Cancer

Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis

Peptides of neuron specific enolase as potential ASD biomarkers: From discovery to epitope mapping

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