Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Liu, Hailong; Deng, Zengfa; Yu, Baoxi; Liu, Hui; Yang, Zhijian; Zeng, Anyu; Fu, Ming

doi:10.3390/cells11213430

Cited by 31 publications

(22 citation statements)

References 40 publications

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“…Identifying potential disease markers of osteoarthritis has been a research hotspot in different aspects. However, most reports only utilized limited, even single, datasets [ 35 , 36 , 37 ]. We believe that merging datasets from different sources could result in a more persuasive conclusion.…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune-Related Risk Genes in Osteoarthritis Based on Bioinformatics Analysis and Machine Learning

Chen

et al. 2023

JPM

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In this research, we aimed to perform a comprehensive bioinformatic analysis of immune cell infiltration in osteoarthritic cartilage and synovium and identify potential risk genes. Datasets were downloaded from the Gene Expression Omnibus database. We integrated the datasets, removed the batch effects and analyzed immune cell infiltration along with differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to identify the positively correlated gene modules. LASSO (least absolute shrinkage and selection operator)-cox regression analysis was performed to screen the characteristic genes. The intersection of the DEGs, characteristic genes and module genes was identified as the risk genes. The WGCNA analysis demonstrates that the blue module was highly correlated and statistically significant as well as enriched in immune-related signaling pathways and biological functions in the KEGG and GO enrichment. LASSO-cox regression analysis screened 11 characteristic genes from the hub genes of the blue module. After the DEG, characteristic gene and immune-related gene datasets were intersected, three genes, PTGS1, HLA-DMB and GPR137B, were identified as the risk genes in this research. In this research, we identified three risk genes related to the immune system in osteoarthritis and provide a feasible approach to drug development in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of Immune-Related Risk Genes in Osteoarthritis Based on Bioinformatics Analysis and Machine Learning

Chen

et al. 2023

JPM

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“…A complete blood workup, including FBC, aids in identifying anaemia, a potential consequence of bleeding associated with peptic ulcers. Additionally, liver function tests, and levels of amylase and lipase contribute to a comprehensive assessment [61].…”

Section: Full Blood Count (Fbc)mentioning

confidence: 99%

Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review

Joshi,

Kumar

et al. 2024

Horm Metab Res

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Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5–10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.

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“…To verify the expression of RBPs in melanocytes further, we obtained bulk RNA-seq data from normal (PIG1) and vitiligo (PIG3V) melanocytes [24]. After the quality control and DEG analysis, 3242 upregulated DEGs and 3209 downregulated DEGs were identi ed.…”

Section: Functional Rbps Are Largely Regulated In Melanocytes Between...mentioning

confidence: 99%

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Zhang,

Xiang,

Ding

et al. 2023

Preprint

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Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Methods Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. We analyzed the RBP genes in different cell subpopulations, especially melanocytes. Combined with the bulk RNA-seq data of melanocytes, we obtained the different RBP genes from melanocytes and predicted their function. Cell experiments, including gene knockdown, qRT–PCR, western blotting, flow cytometry, oxidative stress, and ferroptosis-related tests, were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Results We identified 14 different cell types and 28 cell subpopulations using scRNA-seq data. There is a significant difference in the proportion of each cell subpopulation between the patients with vitiligo and healthy groups. The RBP gene expression is highly heterogeneous; there are significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there are no significant differences in other cells, such as T cells and fibroblasts in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo group. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including 11 upregulated RBP genes (BST2, CDKN2A, HLA-A, IFIT1, LMF2, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments confirmed melanocyte proliferation decreased, whereas apoptosis increased after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of GSH and GPX4. Conclusions We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

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Identification of SLC3A2 as a Potential Therapeutic Target of Osteoarthritis Involved in Ferroptosis by Integrating Bioinformatics, Clinical Factors and Experiments

Cited by 31 publications

References 40 publications

Identification of Immune-Related Risk Genes in Osteoarthritis Based on Bioinformatics Analysis and Machine Learning

Identification of Immune-Related Risk Genes in Osteoarthritis Based on Bioinformatics Analysis and Machine Learning

Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

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