Drug-Loaded Biomimetic Carriers for Non-Hodgkin's Lymphoma Therapy: Advances and Perspective.

Chemotherapy remains the mainstay of treatment for the lymphoma patient population, despite its relatively poor therapeutic results, high toxicity, and low specificity. With the advancement of biotechnology, the significance of drug-loading biomimetic materials in the medical field has become increasingly evident, attracting extensive attention from the scientific community and the pharmaceutical industry. Given that they can cater to the particular requirements of lymphoma patients, drug-loading biomimetic materials have recently become a potent and promising delivery approach for various applications. This review mainly reviews the recent advancements in the treatment of tumors with biological drug carrier-loaded drugs, outlines the mechanisms of lymphoma development and the diverse treatment modalities currently available, and discusses the merits and limitations of biological drug carriers. What is more, the practical application of biocarriers in tumors is explored by providing examples, and the possibility of loading such organisms with antilymphoma drugs for the treatment of lymphoma is conceived.

B7-H7: A potential target for cancer immunotherapy.

Cancer immunotherapy enhances the body's immunity against tumors by mitigating immune escape. Compared with traditional chemotherapy, immunotherapy has the advantages of fewer drugs, a wider range of action and fewer side effects. B7-H7 (also known as HHLA2, B7y) is a member of the B7 family of costimulatory molecules that was discovered more than 20 years ago. B7-H7 is mostly expressed in organs such as the breast, intestine, gallbladder and placenta and is detected predominantly in monocytes/macrophages in the immune system. Its expression is upregulated after stimulation by inflammatory factors such as lipopolysaccharide and interferon-γ. B7-H7/transmembrane and immunoglobulin domain containing 2 (TMIGD2) and killer cell immunoglobulin-like receptor, three Ig domains and long cytoplasmic tail 3 (KIR3DL3)-B7-H7 are the two currently confirmed signaling pathways for B7-H7. An increasing number of studies have demonstrated that B7-H7 is widely present in a variety of human tumor tissues, especially in programmed cell death-1 (PD-L1)-negative human tumors. B7-H7 promotes tumor progression, disrupts T-cell-mediated antitumor immunity, and inhibits immune surveillance. B7-H7 also triggers tumor immune escape and is associated with clinical stage, depth of tumor infiltration, metastasis, prognosis, and survival related to different tumor types. Multiple studies have shown that B7-H7 is a promising immunotherapeutic target. Herein, review the current literature on the expression, regulation, receptors and function of B7-H7 and its regulation/function in tumors.

RNA-seq analysis reveals candidate genes associated with proliferation, invasion, and migration in BCL11A knockdown B-NHL cell lines.

B-cell lymphoma/leukemia 11A (BCL11A) is highly expressed in B-cell non-Hodgkin lymphoma (B-NHL), blocks cell differentiation, and inhibits cell apoptosis. However, little is known about BCL11A in the proliferation, invasion, and migration of B-NHL cells. Here, we found increased expression of BCL11A in B-NHL patients and cell lines. Knockdown of BCL11A suppressed the proliferation, invasion, and migration of B-NHL cells in vitro and reduced tumor growth in vivo. RNA sequencing (RNA-seq) and KEGG pathway analysis demonstrated that BCL11A-targeted genes were significantly enriched in the PI3K/AKT signaling pathway, focal adhesion, and extracellular matrix (ECM)-receptor interaction (including COL4A1, COL4A2, FN1, SPP1), and SPP1 was the most significantly downregulated gene. qRT‒PCR, western blotting, and immunohistochemistry revealed that silencing BCL11A reduced the expression level of SPP1 in Raji cells. Our study suggested that high level of BCL11A may promote B-NHL proliferation, invasion, and migration, and the BCL11A-SPP1 regulatory axis may play an important role in Burkitt's lymphoma.

Corrigendum: RAB42 promotes glioma pathogenesis via the VEGF signaling pathway.

[This corrects the article DOI: 10.3389/fonc.2021.657029.].

RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway.

Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways.

Prognostic Value of Eight-Gene Signature in Head and Neck Squamous Carcinoma.

Head and neck cancer (HNC) is the fifth most common cancer worldwide. In this study, we performed an integrative analysis of the discovery set and established an eight-gene signature for the prediction of prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Univariate Cox analysis was used to identify prognosis-related genes (with P < 0.05) in the GSE41613, GSE65858, and TCGA-HNSC RNA-Seq datasets after data collection. We performed LASSO Cox regression analysis and identified eight genes (CBX3, GNA12, P4HA1, PLAU, PPL, RAB25, EPHX3, and HLF) with non-zero regression coefficients in TCGA-HNSC datasets. Survival analysis revealed that the overall survival (OS) of GSE41613 and GSE65858 datasets and the progression-free survival(DFS)of GSE27020 and GSE42743 datasets in the low-risk group exhibited better survival outcomes compared with the high-risk group. To verify that the eight-mRNA prognostic model was independent of other clinical features, KM survival analysis of the specific subtypes with different clinical characteristics was performed. Univariate and multivariate Cox regression analyses were used to identify three independent prognostic factors to construct a prognostic nomogram. Finally, the GSVA algorithm identified six pathways that were activated in the intersection of the TCGA-HNSC, GSE65858, and GSE41613 datasets, including early estrogen response, cholesterol homeostasis, oxidative phosphorylation, fatty acid metabolism, bile acid metabolism, and Kras signaling. However, the epithelial-mesenchymal transition pathway was inhibited at the intersection of the three datasets. In conclusion, the eight-gene prognostic signature proved to be a useful tool in the prognostic evaluation and facilitate personalized treatment of HNSCC patients.

Continuous epileptic negative myoclonus as the first seizure type in atypical benign epilepsy with centrotemporal spikes.

To figure out which diagnosis is more suitable and which antiepileptic drugs are more sensitive to epileptic negative myoclonus (ENM) as the first seizure type in atypical benign epilepsy with centrotemporal spikes.We reviewed the electroencephalogram (EEG) database of Linyi People's Hospital Affiliated to Shandong University and medical records of patients with ENM onset. The characteristics of epileptic seizures, onset age, treatment process, growth and development history, past disease history, family history, degree of mental deterioration, cranial imaging, and video-EEG were studied retrospectively and followed up.There were 4 cases with ENM onset and 1 with continuous ENM, 3 males and 1 female. The onset age was from 2 years 3 months to 8 years 7 months. The cranial magnetic resonance imaging (MRI) and developmental quotient, as well as the family, personal, and past disease history, were normal. Frequent falls and drops were the main clinical manifestations. Five months after the onset of ENM, case 1 had focal seizures in sleep. ENM was the first and only manifestation in all the other 3 children. Discharges of interictal EEG were in bilateral rolandic areas, especially in midline areas (Cz, Pz), electrical status epilepticus in sleep was found in 3 cases. One child was sensitive to levetiracetam, the other 3 were sensitive to clonazepam.ENM can affect the upper or lower extremities. ENM as the first or only symptom was a special phenomenon in benign epilepsy with centrotemporal spikes (BECTS) variants. Ignorance of midline spikes mainly in Cz or Pz in BECTS might lead to missed diagnosis of ENM. Whether benzodiazepines are viable as a choice of BECTS variants with electrical status epilepticus in sleep when ENM is the first symptom still needs a large sample evidence-based observation.

Association of SCN1A, SCN2A, and UGT2B7 Polymorphisms with Responsiveness to Valproic Acid in the Treatment of Epilepsy.

PURPOSE: The efficacy of valproic acid (VPA) varies widely in clinical treatment of epileptic patients. Our study is aimed at exploring a potential association between polymorphisms of SCN1A, SCN2A, and UGT2B7 genetic factors and VPA responses. METHODS: In this observational study, a total of 114 epileptic patients only treated with VPA for at least 1 year were included to explore the genetic polymorphisms of drug responses (mean follow-up time: 3.68 ± 1.78 years). Thirty-one single-nucleotide polymorphisms (SNPs) in three candidate genes that related with drug-metabolizing enzymes and receptors were genotyped. RESULTS: Of the 31 SNPs, eight were significantly associated with VPA responses, including rs1381105, rs2162600, rs10197716, rs2119068, rs2119067, rs353116, rs353112 and rs6740895. The interaction between rs10197716 and rs2119068 was the most significantly correlated with VPA responses compared with other combinations (the highest VPA-responsive rate 0.92 versus the lowest VPA-responsive rate 0.33, p = 0.007). CONCLUSION: The study indicated that eight SNPs and SNP-SNP interaction may be associated with VPA responses in Chinese Han epileptic patients. The SNPs were rs1381105 (SCN1A), rs2162600 (SCN1A), rs10197716 (SCN2A), rs2119068 (SCN2A), rs2119067 (SCN2A), rs353116 (SCN2A), rs353112 (SCN2A) and rs6740895 (SCN2A), respectively. The interaction between the three pairs of rs10197716-rs2119068, rs10197716-rs11889342 and rs7598931-rs12233719 was the most significant for VPA. This implied that these SNPs may play an important role in the pharmacogenomics mechanism of valproic acid.

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy.

BACKGROUND: PCDH19 has become the second most relevant gene in epilepsy after SCN1A. Seizures often provoked by fever. METHODS: We screened 152 children with fever-sensitive epilepsy for gene detection. Their clinical information was followed up. RESULTS: We found eight PCDH19 point mutations (four novel and four reported) and one whole gene deletion in 10 female probands (seven sporadic cases and three family cases) who also had cluster seizures. The common clinical features of 16 patients in 10 families included fever-sensitive and cluster seizures, mainly focal or tonic-clonic seizures, and absence of status epilepticus, normal intelligence, or mild-to-moderate cognitive impairment, the onset age ranges from 5 months to 20 years. Only four patients had multiple or focal transient discharges in interictal EEG. Focal seizures originating in the frontal region were recorded in four patients, two from the parietal region, and one from the occipital region. CONCLUSION: PCDH19 mutation can be inherited or de novo. The clinical spectrum of PCDH19 mutation includes PCDH19 Girls Clustering Epilepsy with or without mental retardation, psychosis, and asymptomatic male. The onset age of PCDH19 Girls Clustering Epilepsy can range from infancy to adulthood. Sisters in the same family may be sensitive to the same antiepileptic drugs. And our report expands the mutation spectrum of PCDH19 Girls Clustering Epilepsy.

Diagnostic and Prognostic Potential of Serum Cell-Free microRNA-214 in Glioma.

OBJECTIVE: We aimed to expound feasibility of serum cell-free microRNA-214 (miR-214) as a noninvasive biomarker for glioma in this study. PATIENTS AND METHODS: We detected expression of miR-214 in medium from 2 glioma cell lines to confirm whether it is secretory in screening phase. Then, we verified cell-free miR-214 expression in serum samples from an independent set of 100 preoperative patients with glioma, 30 matching postoperative patients, and 100 healthy controls. RESULTS: MiR-214 was secreted from glioma cell lines. Extracellular miR-214 levels were significantly overexpressed in preoperative serum from glioma patients with glioma, whereas its expression significantly decreased in matched postoperative serum. Upregulated cell-free miR-214 in serum was significantly associated with higher tumor grade, absence of isocitrate dehydrogenase, and unmethylated methylguanine methyltransferase promoter. Extracellular miR-214 in serum could effectively distinguish patients with glioma from healthy control (area under the curve = 0.885; 95% confidence interval, 0.833-0.926). Moreover, serum cell-free miR-214 was an independent prognostic indicator of overall survival for patients with glioma. CONCLUSIONS: Serum cell-free miR-214 could serve as a promising noninvasive biomarker of glioma in tumor stratification, early diagnosis, and prognostic evaluation.

Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid ß induced neurotoxicity.

We examined synergistic effects of inhibiting reactive oxygen species generated from the mitochondria and from nicotinamide adenine dinucleotide phosphate oxidase on neurotoxicity. Primary hippocampal neurons were exposed to amyloid ß, and the cells were treated with diazoxide or/and diphenyleneiodonium chloride. We found that the cell viability was decreased significantly after exposure to amyloid ß for 72 h with higer reactive oxygen species and malondialdehyde levels, higher caspase-3 and cleaved caspase-3 levels and lower B-cell lymphoma 2 (Bcl-2) level. Both diazoxide and diphenyleneiodonium increased cell viability by inhibiting the increase in reactive oxygen species and caspase-3 activity as well as the decrease in Bcl-2 induced by amyloid ß. The combination of diazoxide and diphenyleneiodonium exhibited better protective effects compared to a single treatment. In conclusion, the activation of a mitochondrial potassium channel in combination with the inhibitor of nicotinamide adenine dinucleotide phosphate oxidase exhibit synergistic protective effects against amyloid ß neurotoxicity.

Mitochondrial DNA analyses found five novel mutations in idiopathic epilepsy patients.

Epilepsy is a common and chronic neurological disease with a high degree of genetic heterogeneity. The etiology and pathogenesis of the disease have not been fully understood. Many studies suggested that there was a reciprocal relationship between mitochondrial dysfunction and epilepsy, but few studies focused on the mitochondrial genome (mtDNA) of the epilepsy patient which was extremely important for the mitochondrial function. In our study, we obtained complete mtDNA sequences of 27 idiopathic epilepsy patients and healthy people, and compared the sequence data with 30,000 GenBank sequences including 277 Han Chinese mtDNA sequences. We analyzed each variant that might be related to disease and examined the statistically significant variant in more than 300 patients and healthy people. Ultimately, we identified 27 variants which were reported to be associated with diseases, 4 rare variants (321T > G, 15973 T > C, 3897C > A, 12580 C > T), and a nonsynonymous variant (3571 C > T) which was predicted to be damaging. Although no variant was found to be significantly associated with epilepsy, our study provided a new insight into epilepsy study on an aspect of the mitochondrial genome.

B7-H6 expression is induced by lipopolysaccharide and facilitates cancer invasion and metastasis in human gliomas.

Although great progress has been made in treatment regimens, gliomas are still incurable and the 5-year survival remains poor. Studies focusing on molecules that regulate tumorigenesis or tumor immunity may provide potential therapeutic strategies for patients with glioma. B7-H6 is selectively expressed in tumor cells and plays vital roles in host immune responses. In this study, we demonstrated that B7-H6 was expressed in glioma cell lines, including CRT, U251, SHG-44, SF-295, TG-905 and U373, and tumor tissues isolated from glioma patients. Moreover, the expression levels of B7-H6 were significantly correlated with glioma grade. Previous studies reported that inflammatory mediators and cytokines induced the expression of B7 family members including programmed death-ligand 1, B7-H2 and B7-H4. Therefore, we explored the regulation of B7-H6 expression in gliomas and showed that lipopolysaccharide induced the expression of B7-H6 in glioma cells. To further analyze the roles of B7-H6 in gliomas, the expression of B7-H6 in glioma cells was knocked down. The results of cell counting kit-8, colony formation, wound healing, and transwell migration and invasion assays demonstrated that the proliferation, migration and invasion of glioma cells were inhibited after knocking down B7-H6. To elucidate the specific mechanisms of B7-H6 function in cancer progression, we examined the expression levels of proteins involved in cell apoptosis, migration and invasion. We demonstrated that the expression levels of E-cadherin and Bcl-2 associated X protein increased, and the expression levels of vimentin, N-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9 and survivin decreased after knocking down B7-H6. In conclusion, B7-H6 plays important roles in glioma, and targeting B7-H6 may provide a novel therapeutic strategy for glioma patients.

Effects of epigallocatechin­3­gallate on iron metabolism in spinal cord motor neurons.

Accumulating evidence suggests that iron homeostasis is disordered in amyotrophic lateral sclerosis (ALS). In view of the promising performance of epigallocatechin­3­gallate (EGCG) in neuroprotection studies, the present study aimed to verify whether EGCG protects motor neurons in an ALS model, and whether it has any effects on iron metabolism using an ELISA and western blotting. The results demonstrated that EGCG decreased oxidative stress and protected motor neurons in the organotypic culture of the rat spinal cord. Furthermore, total iron levels increased significantly in the spinal cord following 3 weeks of treatment with threo­hydroxyaspartate. In addition, the expression of influx proteins (transferrin receptor and divalent metal­ion transporter 1) increased significantly. However, EGCG demonstrated no effect on total iron levels and the expression of influx proteins. In conclusion, EGCG leads to a decrease in oxidative stress levels, leading to motor neuron protection in the organotypic culture of a rat spinal cord; however, EGCG does not alter iron metabolism protein expression regulation.

CD44+ fibroblasts increases breast cancer cell survival and drug resistance via IGF2BP3-CD44-IGF2 signalling.

CD44, a cell adhesion protein, involves in various process in cancer such as cell survival and metastasis. Most researches on CD44 in cancer focus on cancer cells. Recently, it is found that CD44 expression is high in fibroblasts of tumour microenvironment. However, its role in communication between fibroblasts and breast cancer cells is seldom known. In this study, CD44-positive (CD44+ Fbs) and CD44-negative carcinoma-associated fibroblasts (CD44- Fbs) were isolated and cocultured with breast cancer cells for analysis of cell survival and drug resistance. We found that CD44+ Fbs promoted breast cancer cell survival and paclitaxel resistance and inhibited paclitaxel-induced apoptosis. Our further research for the molecular mechanism showed that IGF2BP3 bound to CD44 mRNA and enhanced CD44 expression, which increased IGF2 levels of fibroblasts and then stimulated breast cancer cell proliferation and drug resistance. IGF2 was found to activate Hedgehog signal pathway in breast cancer cells. In conclusion, the results illustrated that in CD44+ Fbs, binding of IGF2BP3 and CD44 promotes IGF2 expression and then accelerates breast cancer cell proliferation, survival and induced chemotherapy resistance likely by activating Hedgehog signal pathways.

Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer.

Carcinoma associated fibroblasts (CAFs) play important roles in breast cancer development and progression. Recent studies show that microRNAs (miRNAs) are the main regulators in CAFs. MiR-29b is one of the significant down-regulated miRNAs in CAFs from the miRNA screening. The role of miR-29b in the interaction between CAFs and breast cancer is still unclear. In the present study, we investigated the effects of CAFs on breast cancer cell proliferation and metastasis regulated by miR-29b. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of some chemokines like CCL11, CXCL14, which accelerated breast cancer cell growth and induced drug resistance and metastasis. Increased miR-29b expression in activated fibroblasts could suppress the activating p38-STAT1 signal pathway in breast cancer cells. We also found that the expression of CCL11 and CXCL14 could be regulated by miR-29b in CAFs. Our results illustrate that down-regulation of miR-29b in CAFs plays an important role in tumor stroma by activating p38-STAT1 in breast cancer cells. The study indicates that cancer cells and fibroblasts interaction promotes breast cancer cell growth, drug resistance, migration and invasion due to the lack of miR-29b expression in CAFs.

Novel B7-H4-mediated crosstalk between human non-Hodgkin lymphoma cells and tumor-associated macrophages leads to immune evasion via secretion of IL-6 and IL-10.

Non-Hodgkin lymphoma (NHL) is an incurable lymphoproliferative cancer, and patients with NHL have a poor prognosis. The present study explored the regulatory mechanism of expression and possible roles of the immunosuppressive B7-H4 molecule in human NHL. For functional studies, NHL-reactive T cell lines were generated via the isolation of allogeneic CD3+ T cells from healthy donors and repeated in vitro stimulation with irradiated NHL cells isolated from patients. B7-H4 was found to be distributed in NHL cells and tissues, and its surface protein expression levels were further upregulated by the incubation of NHL cells with interleukin (IL)-6, IL-10, or interferon-γ. Additionally, the supernatants of tumor-associated macrophages (tMφs) upregulated B7-H4 surface expression by producing IL-6 and IL-10. B7-H4 expressed in NHL cells inhibited the cytotoxic activity of NHL-reactive T cells. Conversely, the inhibition of B7-H4 in NHL cells promoted T cell immunity and sensitized NHL cells to cytolysis. Furthermore, tMφs induced B7-H4 promoted NHL cell evasion of the T cell immune response. In conclusion, this study shows that NHL-expressed B7-H4 is an important immunosuppressive factor that inhibits host anti-tumor immunity to NHL. Targeting tumor-expressed B7-H4 may thus provide a new treatment strategy for NHL patients.

miR-137 regulates the migration of human umbilical vein endothelial cells by targeting ephrin-type A receptor 7.

MicroRNAs (miRNAs) are short non-coding RNAs, which negatively regulate gene expression. Post­transcriptional regulation by miRNAs is important for organism development. In addition, endothelial cells are key regulators of angiogenesis. By using the 3-(4,5-dimethylthiazol-2-yl)­2,5­diphenyltetrazolium bromide (MTT), migration and gelatin sponge-chorioallantoic membrane assays, it was demonstrated that when miR-137 was overexpressed, cell viability and migration decreased. In addition, it was observed that blocking endogenous miR-137 increased cell viability and migration. Bioinformatics analysis indicated that the 3'­untranslated region (3'UTR) of the ephrin type-A receptor 7 (EPHA7) has a putative binding site for miR-137. miR-137 is able to directly bind to the EPHA7 3'UTR and negatively regulate the expression of EPHA7. miR-137 is also able to decrease the growth and migration of human umbilical vein endothelial cells (HUVECs). The identification of the function of miR-137 and its target gene EPHA7 in HUVECs may provide novel insights into the mechanisms of angiogenesis.

Increased iron level in motor cortex of amyotrophic lateral sclerosis patients: an in vivo MR study.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative disorders, but no definite mechanism has been defined on the loss of motor neurons in ALS and currently no therapy can block its progression. Many lines of evidence indicate that there is a disorder of iron homeostasis in ALS, and thus we sought to test the iron level in ALS patients by susceptibility weighted imaging (SWI). Sixteen ALS patients and 16 healthy persons underwent brain scans using SWI with a 3T Siemens MR scanner. The red nucleus, substantia nigra, globus pallidus, putamen, the head of caudate nucleus, and motor cortex were measured in the filtered phase images and analysed for their SWI phase values as relative marker for iron content. We found that phase shift values were significantly higher in the motor cortex of ALS patients by SWI, indicating increased iron level in this area. In contrast, we found that there were no differences of phase shift values between ALS patients and healthy controls in the other nuclei including the red nucleus, substantia nigra, globus pallidus, putamen and the head of the caudate nucleus. Furthermore, we found that there were no relationships between SWI signal and some clinical features of ALS. In conclusion, these results demonstrate that iron level increases in the motor cortex of ALS and that SWI is a reliable method to test iron in the brain.

Effect of the human SOD1-G93A gene on the Nrf2/ARE signaling pathway in NSC-34 cells.

Dominant mutations in superoxide dismutase 1 (SOD1) are a frequent cause of the lethal neurodegenerative disease amyotrophic lateral sclerosis (ALS). The nuclear factor erythroid 2­related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is the major cellular defense mechanism against oxidative stress, however, its role in ALS remains to be fully elucidated. Therefore, the present study aimed to investigate whether the human SOD1-G93A gene affected the Nrf2/ARE signaling pathway in an ALS cell model. The soma became round and the number of neurites decreased in the NSC-34 cells transfected with the hSOD1-G93A gene, and the neurites were shorter and oxidative stress was increased compared with the normal NSC-34 cells. Furthermore, the mRNA and protein expression of Nrf2, heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 was significantly decreased in the NSC-34 cells transfected with the human SOD1-G93A gene. The present study indicated that human SOD1-G93A damaged the Nrf2/ARE signaling pathway in the ALS cell model and reduced the ability of cells to protect against oxidative injury.