Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis

Mao, Jingyi; Ma, Xiaoguang

doi:10.1155/2022/3818216

Cited by 10 publications

(3 citation statements)

References 46 publications

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“…Moreover, Choudhary et al utilized GSE78097 dataset to identify biomarkers for mild and severe psoriasis by comparing gene expression between lesional and non-lesional skin [39]. Additionally, GSE13355 and GSE14905 are two gene datasets extensively used for psoriasis research contributing to numerous studies [40,41].…”

Section: Discussionmentioning

confidence: 99%

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy

Li,

Wang,

Zhu

et al. 2024

Biomol Biomed

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Psoriasis is a globally prevalent chronic inflammatory skin disease. This study aimed to scrutinize the hub genes related to inflammation and potential molecular mechanisms in psoriasis. Utilizing mRNA expression profiles from public datasets GSE13355, GSE78097, and GSE14905, we set up a comprehensive analysis. Initially, we selected differentially expressed genes (DEGs) from psoriasis and control samples in GSE13355, followed by calculating inflammatory indices using genomic set variation analysis (GSVA). Weighted gene co-expression network analysis (WGCNA) was then applied to link significant modules with the inflammatory index. This process helped us identify differentially expressed inflammation-related genes (DE-IRGs). A protein-protein interaction (PPI) network was established, with the molecular complex detection (MCODE) plug-in pinpointing six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as central hub genes. These genes demonstrated pronounced immunohistochemical staining in psoriatic tissues compared to normal skin. Notably, the CCR7 gene exhibited the highest potential for m6A modification sites. Furthermore, we constructed transcription factor-microRNA-mRNA networks, identifying 139 microRNAs and 52 transcription factors associated with the hub genes. For the LASSO logistic regression model, the area under the curve (AUC) in the training set was 1, and in the two validation cohorts GSE78097 and GSE14905 were 1 and 0.872, respectively. In conclusion, our study highlights six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as potential biomarkers in psoriasis, providing insights into the immune and inflammatory responses as pivotal instances in disease pathogenesis. These findings pave the way for exploring new therapeutic targets, particularly focusing on chemokine-associated pathways in psoriasis treatment.

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Section: Discussionmentioning

confidence: 99%

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy

Li,

Wang,

Zhu

et al. 2024

Biomol Biomed

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“…SLC7A5 together with SLC3A2 mediate cellular uptake of the large neutral amino acids, phenylalanine, tyrosine, leucine, and tryptophan ( Mastroberardino et al, 1998 ). SLC7A5 may affect the development of many diseases by regulating ferroptosis ( Mao and Ma, 2022 ). Signal Transducer and Activator of Transcription 3 (STAT3) is a member of the STAT protein family.…”

Section: Discussionmentioning

confidence: 99%

A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy

et al. 2023

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Objective: Cardiac dysfunction caused by sepsis, usually termed sepsis-induced cardiomyopathy (SIC), is one of the most serious complications of sepsis, and ferroptosis can play a key role in this disease. In this study, we identified key cuproptosis- and ferroptosis-related genes involved in SIC and further explored drug candidates for the treatment of SIC.Methods: The GSE79962 gene expression profile of SIC patients was downloaded from the Gene Expression Omnibus database (GEO). The data was used to identify differentially expressed genes (DEGs) and to perform weighted correlation network analysis (WGCNA). Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Then, gene set enrichment analysis (GSEA) was applied to further analyze pathway regulation, with an adjusted p-value <0.05 and a false discovery rate (FDR) <0.25. Ferroptosis-related genes were obtained from the FerrDb V2 database, and cuproptosis-related genes were obtained from the literature. We constructed a novel signature (CRF) by combing cuproptosis-related genes with ferroptosis-related genes using the STRING website. The SIC hub genes were obtained by overlapping DEGs, WGCNA-based hub genes and CRF genes, and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of hub genes. A transcription factor-microRNA-hub gene network was also constructed based on the miRnet database. Finally, potential therapeutic compounds for SIC were predicted based on the Drug Gene Interaction Database.Results: We identified 173 DEGs in SIC patients. Four hub modules and 411 hub genes were identified by WGCNA. A total of 144 genes were found in the CRF. Then, POR, SLC7A5 and STAT3 were identified as intersecting hub genes and their diagnostic values were confirmed with ROC curves. Drug screening identified 15 candidates for SIC treatment.Conclusion: We revealed that the cuproptosis- and ferroptosis-related genes, POR, SLC7A5 and STAT3, were significantly correlated with SIC and we also predicted therapeutic drugs for these targets. The findings from this study will make contributions to the development of treatments for SIC.

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“…Given the pathophysiological mechanisms of hyperproliferative skin conditions, these effects might be potentially beneficial to treat them. In addition, it has been predicted that RLZ may inhibit xCT (Cystine/glutamate transporter), a ferroptosis-associated gene highly expressed in psoriasis [14]. Of note, keratinocytes express components of the glutamate signaling pathway [15].…”

Section: Introductionmentioning

confidence: 99%

Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases

Llorente

Bonilla

Agudelo

et al. 2023

IJMS

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Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.

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Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis

Cited by 10 publications

References 46 publications

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy

A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy

Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases

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