Effect of Sun exposure-induced ferroptosis mechanisms on pathology and potential biological processes of primary melanoma by microarray data analysis

Abstract

Objectives: Sunlight exposure is an important environmental factor in the pathogenesis of skin cutaneous melanoma (SKCM). Ultraviolet (UV) from sunlight can cause excessive intracellular production of reactive oxygen species (ROS), resulting in damage from oxidative stress to cells. As a major iron-rich and ROS-producing organelle, mitochondria are considered as an important place for cell ferroptosis. Thus, the pathology and potential biological process of UV exposure-induced ferroptosis in the development of SKCM has aroused our strong interest.Methods: Gene expression profile datasets of melanoma cell line datasets (GSE31909) and UV-irradiated mitochondria dataset (GSE3632) were downloaded from the Gene Expression Omnibus (GEO) database, and ferroptosis-related genes were obtained from the FerrDb v2 database. After identifying the common differentially expressed genes (DEGs), comprehensive analyzes were performed, including functional annotation, protein-protein interaction (PPI) network construction, hub gene identification, and gene and tissue protein expression levels, survival analysis, and immune cell infiltration analysis.Results: A total of 14 common DEGs was identified for subsequent analyses. Seven DEGs, including PSMB4, CRELD2, CDKN2A, TIMP1, NDRG1, ATF3 and JUND, have consistent performance in mRNA and protein expression in normal skin and SKCM tissues can be regarded as a good biomarker with SKCM diagnostic effectiveness. Functional enrichment analysis results indicate that HIF-1 signaling pathway and angiogenesis involved in the pathogenesis and development of SKCM. Induction of ferroptosis in tumor cells by enhancing the function of CD8+ T cells is expected to be an effective intervention to promote tumor therapy.Conclusion: Our study reveals the pathogenesis and potential biological processes of UV exposure-induced ferroptosis in the development of SKCM, which may provide potential immunotherapy targets for SKCM treatment via tumor cell ferroptosis mechanisms.

Explore the impact of hypoxia-related genes (HRGs) in Cutaneous melanoma

“…When combined with other genes, FBP1 can be used to predict the immune microenvironment of CM [ 23 , 39 ]. N-Myc Downstream Regulated 1 (NDRG1), a common tumor risk factor, is a powerful immune-related gene in CM and is associated with the ferroptosis pathway [ 24 , 40 ]. Plakophilin 1 (PKP1) is overexpressed in metastatic melanoma and is a factor of poor prognosis in patients with CM, suggesting a link between PKP1 gene expression and immune efficacy [ 27 ].…”

Research progress and insights on the role of ferroptosis in wound healing

“…However, this pathological process can be alleviated by GSH recruitment using nicotinamide mononucleotide 69 . Furthermore, excessive UV exposure can also lead to ROS accumulation in skin, thus inducing ferroptosis by lipid peroxidation mechanism 70 . Taken together, excessive UV exposure can induce ferroptosis by GSH deprivation mechanism, GPX4 mechanism and lipid peroxidation mechanism.…”

“… 69 Furthermore, excessive UV exposure can also lead to ROS accumulation in skin, thus inducing ferroptosis by lipid peroxidation mechanism. 70 Taken together, excessive UV exposure can induce ferroptosis by GSH deprivation mechanism, GPX4 mechanism and lipid peroxidation mechanism. Hence, in UV‐driven wound, caused by frequent ferroptosis, weak capacity to keep redox homeostasis and high rate of cell death led to the impairment of DNA repair and dysregulation of wound healing‐related genes (e.g.…”