Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis

Zheng, Xiangjin; Chen, Wenlin; Yi, Jie; Li, Wan; Liu, Jinyi; Fu, Weiqi; Ren, Liwen; Li, Sha; Ge, Bin‐Bin; Yang, Yihui; Zhang, Yizhi; Yang, Hong; Du, Guanhua; Wang, Yu; Wang, Jinhua

doi:10.1038/s41401-022-00917-3

Cited by 37 publications

(20 citation statements)

References 54 publications

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“…Lipid metabolism disorders and immunoinflammatory responses are critical in the development and progression of DN (30,31), which means that APOC1 may be also involved in the development of DN. APOC1 has been implicated in the progress of many diseases such as malignancy (32), atherosclerosis (33), and Alzheimer's disease (34). More importantly, APOC1 is closely associated with cell proliferation, apoptosis, and immune inflammation (35).…”

Section: Discussionmentioning

confidence: 99%

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

Wang

et al. 2023

Front. Endocrinol.

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IntroductionDiabetic nephropathy is the leading cause of end-stage renal disease, which imposes a huge economic burden on individuals and society, but effective and reliable diagnostic markers are still not available.MethodsDifferentially expressed genes (DEGs) were characterized and functional enrichment analysis was performed in DN patients. Meanwhile, a weighted gene co-expression network (WGCNA) was also constructed. For further, algorithms Lasso and SVM-RFE were applied to screening the DN core secreted genes. Lastly, WB, IHC, IF, and Elias experiments were applied to demonstrate the hub gene expression in DN, and the research results were confirmed in mouse models and clinical specimens.Results17 hub secretion genes were identified in this research by analyzing the DEGs, the important module genes in WGCNA, and the secretion genes. 6 hub secretory genes (APOC1, CCL21, INHBA, RNASE6, TGFBI, VEGFC) were obtained by Lasso and SVM-RFE algorithms. APOC1 was discovered to exhibit elevated expression in renal tissue of a DN mouse model, and APOC1 is probably a core secretory gene in DN. Clinical data demonstrate that APOC1 expression is associated significantly with proteinuria and GFR in DN patients. APOC1 expression in the serum of DN patients was 1.358±0.1292μg/ml, compared to 0.3683±0.08119μg/ml in the healthy population. APOC1 was significantly elevated in the sera of DN patients and the difference was statistical significant (P > 0.001). The ROC curve of APOC1 in DN gave an AUC = 92.5%, sensitivity = 95%, and specificity = 97% (P < 0.001).ConclusionsOur research indicates that APOC1 might be a novel diagnostic biomarker for diabetic nephropathy for the first time and suggest that APOC1 may be available as a candidate intervention target for DN.

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Section: Discussionmentioning

confidence: 99%

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

Wang

et al. 2023

Front. Endocrinol.

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“…The low expression level of CBS is associated with poor survival in cancers with CBS as a tumor suppressor [ 41 ]. Zheng et al reported that Apolipoprotein C1 could facilitate glioblastoma tumorigenesis by inhibiting CBS-mediated ferroptosis, suggesting that reduced expression may help to maintain glioblastoma cell survival by reducing ferroptosis [ 42 ]. These results suggest that affecting nearby genes is an alternative mechanism by which an SNP modifies disease susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Association of RNA m⁷G Modification Gene Polymorphisms with Pediatric Glioma Risk

Zhu

Chen

et al. 2023

BioMed Research International

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Glioma stemming from glial cells of the central nervous system (CNS) is one of the leading causes of cancer death in childhood. The genetic predisposition of glioma is not fully understood. METTL1-WDR4 methyltransferase complex is implicated in tumorigenesis by catalyzing N7-methylguanosine (m7G) modification of RNA. This study is aimed at determining the association of glioma risk with three polymorphisms (rs2291617, rs10877013, and rs10877012) in METTL1 and five polymorphisms (rs2156315 rs2156316, rs6586250, rs15736, and rs2248490) in WDR4 gene in children of Chinese Han. We enrolled 314 cases and 380 controls from three independent hospitals. Genotypes of these polymorphisms were determined using the TaqMan assay. We found the WDR4 gene rs15736 was significantly associated with reduced glioma risk (GA/AA vs. GG: adjusted odds ratio = 0.63 , 95 % confidence interval = 0.42 − 0.94 , P = 0.023 ) out of the eight studied polymorphisms. Stratified analyses showed that the association of rs15736 with the risk of glioma remained significant in children aged 60 months or older, girls, the subgroups with astrocytic tumors, or grade I + II glioma. We also found the combined effects of five WDR4 gene polymorphisms on glioma risk. Finally, expression quantitative trait locus (eQTL) analyses elucidated that the rs15736 polymorphism was related to the expression level of WDR4 and neighboring gene cystathionine-beta-synthase (CBS). Our finding provided evidence of a causal association between WDR4 gene polymorphisms and glioma susceptibility in Chinese Han children.

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“…The immunomodulatory effect of ApoC1 on macrophages and microglia could help glioma cells to induce an immune escape-like metabolic state. Most recently, this has been underlined by the finding that ApoC1 can reduce the activity of ferroptosis pathways in glioma, thus propagating tumor growth [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

The Mean ApoC1 Serum Level in Postoperative Samples from Neurosurgical Patients Is Lower than in Preoperative Samples and during Chemotherapy

Hilbert

Kuzman

Mueller

et al. 2022

Biology

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Serum levels of apolipoprotein ApoC1 have been described in a number of systemic tumor entities as potential biomarkers, but little is known about ApoC1 in neurosurgical patients. A total of 230 serum samples from 96 patients were analyzed using an ELISA technique. Patient diagnoses comprised 70 glioblastomas WHO IV°, 10 anaplastic astrocytomas III°, one anaplastic oligodendroglioma III°, one oligodendroglioma II°, one diffuse astrocytoma II°, one pilocytic astrocytoma I°, and a single case of a spindle cell tumor without WHO grading, as well as 11 spinal interventions. The mean ApoC1 level of the 230 samples was 132.03 µg/mL (median 86.83, SD 292.91). In the 176 glioblastoma samples, the mean ApoC1 level was 130.0 µg/mL (median 86.23, SD 314.9), which was neither different from the whole group nor from patients with spinal interventions (215.1 μg/mL, median 63.6, SD 404.9). In the postoperative samples, the mean ApoC1 level was significantly lower (85.81 μg/mL) than in the preoperative samples (129.64 μg/mL) and in samples obtained during adjuvant chemotherapy (168.44 μg/mL). While absolute ApoC1 serum levels in a patient do not allow for the distinction between neurosurgical histological entities, future analyses will examine whether the time course of ApoC1 in an individual patient can be related to certain treatment stages.

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Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis

Cited by 37 publications

References 54 publications

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

Association of RNA m⁷G Modification Gene Polymorphisms with Pediatric Glioma Risk

The Mean ApoC1 Serum Level in Postoperative Samples from Neurosurgical Patients Is Lower than in Preoperative Samples and during Chemotherapy

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Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis

Cited by 37 publications

References 54 publications

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment

Association of RNA m7G Modification Gene Polymorphisms with Pediatric Glioma Risk

The Mean ApoC1 Serum Level in Postoperative Samples from Neurosurgical Patients Is Lower than in Preoperative Samples and during Chemotherapy

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Association of RNA m⁷G Modification Gene Polymorphisms with Pediatric Glioma Risk