Update on Glycosphingolipids Abundance in Hepatocellular Carcinoma

Byrne, Frances L.; Olzomer, Ellen M.; Lolies, Nina; Hoehn, Kyle L.; Wegner, Marthe-Susanna

doi:10.20944/preprints202203.0309.v1

Cited by 3 publications

(2 citation statements)

References 64 publications

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“…Similar to GSLs, sulfatide (glycosphingolipid sulfate) is also composed of lipid and sugar components, and its precursor galactosylceramide connects the sulfate ester group to the carbohydrate component in the endoplasmic reticulum (ER) ( 34 ). Elevated expression of sulfatide has been found in many human cancer cell lines and tissues, and can be used as a biomarker of some cancers ( 4 , 35 , 36 ). Abundant sulfatide on the surface of cancer cells is a natural ligand of P-selectin ligand that helps to promote tumor metastasis ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma

Huang

Cai

et al. 2023

Front. Oncol.

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BackgroundHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of HCC through multiple pathways. Our previous study reported the specific molecular mechanism for sulfatide regulation of integrin αV expression and cell adhesion in HCC cells through lncRNA AY927503. Next, it is necessary to identify more sulfatide-related lncRNAs, explore their clinical signifcance, and determine new targeted treatment strategies.MethodsMicroarrays were used to screen a complete set of lncRNAs with different expression profiles in sulfatide-treated cells. Sulfatide-related lncRNAs expression data and corresponding HCC patient survival information were obtained from the The Cancer Genome Atlas (TCGA) database, and the prognosis prediction model was constructed based on Cox regression analysis. Methylated RNA immunoprecipitation with next generation sequencing (MeRIP-seq) was used to detemine the effect of sulfatide on lncRNAs m6A modification. Tumor Immune Estimation Resource (TIMER) and Gene set nnrichment analysis (GSEA) were utilized to enrich the immune and functional pathways of sulfatide-related lncRNAs.ResultsA total of 85 differentially expressed lncRNAs (|Fold Change (FC)|>2, P<0.05) were screened in sulfatide-treated HCC cells. As a result, 24 sulfatide-related lncRNAs were highly expressed in HCC tissues, six of which were associated with poor prognosis in HCC patients. Based on thses data, a sulfatide-related lncRNAs prognosis assessment model for HCC was constructed. According to this risk score analysis, the overall survival (OS) curve showed that the OS of high-risk patients was significantly lower than that of low-risk patients (P<0.05). Notably, the expression difference in sulfatide-related lncRNA NRSN2-AS1 may be related to sulfatide-induced RNA m6A methylation. In addition, the expression level of NRSN2-AS1 was significantly positively correlated with immune cell infiltration in HCC and participated in the peroxisome and Peroxisome proliferator-activated receptor (PPAR) signaling pathways.ConclusionsIn conclusion, sulfatide-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

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Section: Discussionmentioning

confidence: 99%

“…Sulfatide had been demonstrated to be one of several natural ligands for type II CD1d-restricted NKT cells, which can regulate tumor immunity ( 36 , 44 , 45 ). More and more studies have also found the potential effect of lncRNAs on immune cells infiltration in TIME.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma

Huang

Cai

et al. 2023

Front. Oncol.

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The Role of Sphingolipid Metabolism in Pregnancy-Associated Breast Cancer After Chemotherapy

Blokhin,

Zavarykina,

Kotsuba

et al. 2024

Biomedicines

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Background: The aim of our study was to determine the role of sphingolipids, which control proliferation and apoptosis, in the placenta of pregnant women with pregnancy-associated breast cancer (PABC) after chemotherapy compared with healthy patients. Methods: :We analyzed (by the PCR method) the gene expression of key sphingolipid metabolism enzymes (sphingomyelinases (SMPD1 and SMPD3), acid ceramidase (ASAH1), ceramide synthases (CERS 1-6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), and sphingosine-1-phosphate receptors (S1PR1, S1PR2, and S1PR3)) and the content of subspecies of ceramides, sphingosine, and sphingosine-1-phosphate in seven patients with PABC after chemotherapy and eight healthy pregnant women as a control group. Results: We found a significant increase in the expression of genes of acid ceramidase (ASAH1), sphingosine-1-phosphate lyase 1 (SGPL1), sphingosine kinase (SPHK1), and ceramide synthases (CERS 1-3, 5, 6) in the samples of patients with PABC during their treatment with cytostatic chemotherapy. The increase in the expression of the enzymes’ genes was not accompanied by changes in the content of the studied sphingolipids. Such significant changes in the expression of genes controlling the level of CER, sphingosine, and S1P may indicate their ability to initiate the metabolism of pro-apoptotic and anti-apoptotic sphingolipids in the placenta of pregnant women with cancer undergoing chemotherapy in order to maintain levels typical of the placenta of healthy women. Conclusions: Our results may indicate the promising mechanism of placenta protection during chemotherapy for pregnant women with breast cancer and, consequently, of the newborn. This protective effect of the placenta and especially for the newborn has been discovered for the first time and requires more careful study.

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Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells

Seo,

Ju,

Kim

et al. 2024

IJMS

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Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin’s anti-cancer properties and ganglioside expression in melanoma remains incompletely understood. In this study, quercetin manifests specific anti-proliferative, anti-migratory, and cell-cycle arrest effects, inducing mitochondrial dysfunction and apoptosis in two melanoma cancer cell lines. This positions quercetin as a promising candidate for treating malignant melanoma. Moreover, our investigation indicates that quercetin significantly reduces the expression levels of ganglioside GD3 and its synthetic enzyme. Notably, this reduction is achieved through the inhibition of the FAK/paxillin/Akt signaling pathway, which plays a crucial role in cancer development. Taken together, our findings suggest that quercetin may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

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Update on Glycosphingolipids Abundance in Hepatocellular Carcinoma

Cited by 3 publications

References 64 publications

Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma

Prognostic and immunological role of sulfatide-related lncRNAs in hepatocellular carcinoma

The Role of Sphingolipid Metabolism in Pregnancy-Associated Breast Cancer After Chemotherapy

Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells

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