scholarly journals LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3279
Author(s):  
Yuet Ping Kwan ◽  
Melissa Hui Yen Teo ◽  
Jonathan Chee Woei Lim ◽  
Michelle Siying Tan ◽  
Graciella Rosellinny ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cell ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Treatment Options ◽  
Melanoma Metastasis ◽  
Dependent Manner ◽  
Promoting Effect ◽  
Human Patient ◽  
Cell Invasiveness

Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma.

scholarly journals Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis

2020 ◽  
Author(s):  
Yumei Li ◽  
Bifei Li ◽  
Fan Chen ◽  
Weiyu Shen ◽  
Vladimir L. Katanaev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metastatic Melanoma ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Receptor Interaction ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
Core Genes

Abstract Background Metastasis is the leading cause of melanoma mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen for the key core genes and molecular mechanisms related to the metastasis of melanoma. Methods Gene expression profile, GSE8401 including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between metastatic melanoma and primary melanoma were screened using GEO2R. Assays of gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and protein-protein interaction (PPI) were performed to visualize these DEGs through Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools. Top 10 genes with high degree were defined as hub genes. Furthermore, paired post-metastatic melanoma cells and pre-metastatic melanoma cells were established by experimental mouse model of melanoma metastasis to verify the expression of these hub genes. Results 424 DEGs between the metastatic melanoma and primary melanoma were screened, including 60 upregulated genes enriched in ECM-receptor interaction and progesterone-mediated oocyte maturation and 364 downregulated genes enriched in amoebiasis, melanogenesis, and ECM-receptor interaction. CDH1, EGFR, KRT5, COL17A1, KRT14, IVL, DSP, DSG1, FLG and CDK1 were defined as the hub genes. . In addition, paired post-metastatic melanoma cells (A375M) and pre-metastatic melanoma cells (A375) were established and qRT-PCR analysis confirmed the expression of the hub genes during melanoma metastasis. Conclusion This bioinformatic study has provided a deeper understanding of the molecular mechanisms of melanoma metastasis. KRT5, IVL and COL17A1 have emerged as possible biomarkers and therapeutic targets in metastasis of melanoma.

scholarly journals Exploration and Validation of Metastasis-associated Genes for Skin Cutaneous Melanoma

2021 ◽  
Author(s):  
Hong Luan ◽  
Linge Jian ◽  
Ye He ◽  
Tuo Zhang ◽  
Yanna Su ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cutaneous Melanoma ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Primary Melanoma ◽  
Gene Interaction ◽  
Skin Tumor ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
Hub Gene

Abstract Background: Skin cutaneous melanoma is a malignant and highly metastatic skin tumor, and its morbidity and mortality are still rising worldwide. However, the molecular mechanisms that promote melanoma metastasis are unclear. Methods: Two datasets (GSE15605 and GSE46517) were retrieved to identify the differentially expressed genes (DEGs), including 23 normal skin tissues (N), 77 primary melanoma tissues (T) and 85 metastatic melanoma tissues (M). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to explore the functions of the DEGs. The protein–protein interaction (PPI) network was constructed using the STRING tool and Cytoscape software. We used the cytoHubba plugin of Cytoscape to identify the most significant hub genes by five topological analyses (Degree, Bottleneck, MCC, MNC, and EPC). Hub gene expression was validated using the UALCAN website. Clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Finally, we explored the association between metastasis-associated genes and immune infiltrates through the Tumor Immune Estimation Resource (TIMER) database and performed drug-gene interaction analysis using the Drug-Gene Interaction database.Results: A total of 294 specific genes were related to melanoma metastasis and were mainly involved in the positive regulation of locomotion, mitotic cell cycle process, and epithelial cell differentiation. Four hub genes (CDK1, FOXM1, KIF11, and RFC4) were identified from the cytoHubba plugin of Cytoscape. CDK1 was significantly upregulated in metastatic melanoma compared with primary melanoma, and high expression of CDK1 was positively correlated with poor prognosis. We found that CDK1 expression correlated positively with the infiltration levels of macrophage cells (Rho = -0.164, P = 2.02e-03) and neutrophil cells (Rho = 0.269, P = 2.72e-07) in SKCM metastasis. In addition, we identified that CDK1 had a close interaction with 10 antitumor drugs. Conclusions: CDK1 was identified as a hub gene involved in the progression of melanoma metastasis and may be regarded as a therapeutic target for melanoma patients to improve prognosis and prevent metastasis in the future.

scholarly journals The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis

2019 ◽  
Author(s):  
Xiaomeng Zhang ◽  
Lie Yang ◽  
Pacman Szeto ◽  
Youfang Zhang ◽  
Kaushalya Amarasinghe ◽  
...  
Keyword(s):  
Cell Fate ◽  
Melanoma Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Hippo Pathway ◽  
Melanoma Metastasis ◽  
The Hippo Pathway

ABSTRACTMelanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared to most other skin cancers, a feature of melanoma is its high metastatic capacity, although molecular mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of pathway activity in melanoma cells. Hippo-mediated transcriptional activity varied in melanoma cell lines but failed to cluster with known genetic drivers of melanomagenesis such as BRAF and NRAS mutation status. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness. Consistent with this, the central Hippo oncogene, YAP, was both necessary and sufficient for melanoma cell invasion in vitro. In in vivo murine studies, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genes AXL, THBS1 and CYR61 as key mediators of YAP-induced melanoma cell invasion. These data suggest that the Hippo pathway is a critical regulator of melanoma metastasis.

Skp2, a prognostic marker and potential therapeutic target in metastatic melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11034-11034
Author(s):  
G. Wang ◽  
D. Hanniford ◽  
A. Rose ◽  
A. Gaziel ◽  
A. Pavlick ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Primary Melanoma ◽  
Melanoma Metastasis ◽  
Genomic Amplification ◽  
Aberrant Expression ◽  
Skp2 Protein ◽  
Melanoma Patients ◽  
Melanoma Cell Lines

11034 Background: Skp2, a known oncogene, is overexpressed in several types of tumors and is associated with worse recurrence rate and overall survival in primary melanoma patients. Moreover, the anti-proliferative effects of Skp2 siRNA on various tumor cell lines have prompted the preclinical testing of Skp2 small molecule inhibitors. In this study, we assessed the clinical relevance and molecular mechanism(s) underlying Skp2 overexpression in metastatic melanoma patients. Methods: Skp2 protein levels were measured in 122 metastatic melanoma specimens using immunohistochemistry (IHC), and the association between Skp2 overexpression and post-recurrence survival was examined. Moreover, 22 cell lines (2 normal primary melanocytes, 2 primary immortal melanocytes, 4 primary melanoma cell lines, and 18 metastatic melanoma cell lines) were evaluated for Skp2 genomic amplification using Single Nucleotide Polymorphism (SNP) arrays (Affymetrix 6.0) and Skp2 gene expression using mRNA arrays (Affymetrix U133A 2.0) and quantitative RT-PCR. We also screened 18 cell lines for Skp2 mutation by sequencing. Results: Skp2 overexpression, defined as >25% tumor cells, was associated with shorter 3-yr post-recurrence survival (37%) compared to Skp2 expression ≤25% (55%) (HR=1.89, 95%, CI= 1.04, 3.42, p=0.04). Skp2 overexpression was significantly associated with the site of melanoma metastasis: visceral (n= 12; 89%), lymph node (n=49; 36%), brain (n=15; 14%), and soft-tissue (n=36; 6%) (p<0.001). SNP array revealed genomic amplification at the Skp2 locus in 6 (33%) metastatic cell lines and one primary melanoma cell line. Skp2 genomic amplification was associated with increased transcript expression. No Skp2 mutations were identified. Conclusions: Skp2 protein overexpression is associated with worse prognosis in metastasis in melanoma. Our results also support that gene amplification, rather than a Skp2 gene mutation, may be the major mechanism responsible for Skp2 aberrant expression in metastatic melanoma. No significant financial relationships to disclose.

scholarly journals Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling PathwayIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yujia Li ◽  
Shilin Li ◽  
Xiaoqiong Duan ◽  
Yanzhao Chen ◽  
Baihai Jiao ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Treatment Options ◽  
Antiviral Drug ◽  
Infectious Hepatitis ◽  
Type I ◽  
Dependent Manner ◽  
Promoting Effect ◽  
B Virus

Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infectionin vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.

Molecular mechanisms for the growth factor action of gastrin

1997 ◽  
Vol 273 (4) ◽  
pp. G891-G898 ◽  
Author(s):  
Andrea Todisco ◽  
Yoshiaki Takeuchi ◽  
Andrej Urumov ◽  
Junko Yamada ◽  
Vinzenz M. Stepan ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Molecular Mechanisms ◽  
Luciferase Activity ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Luciferase Reporter Gene ◽  
Promoting Effect ◽  
Ar42j Cells ◽  
Gf 109203X ◽  
Growth Promoting

We have previously observed that gastrin has a cholecystokinin B (CCK-B) receptor-mediated growth-promoting effect on the AR42J rat pancreatic acinar cell line and that this effect is paralleled by induction of expression of the early response gene c- fos. We undertook these experiments to elucidate the mechanism for induction of c- fos and the linkage of this action to the trophic effects of gastrin. Gastrin (0.1–10 nM) dose dependently induced luciferase activity in AR42J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element (SRE) of the c- fos promoter. This effect was blocked by the specific CCK-B receptor antagonist D2 but not by the specific CCK-A receptor antagonist L-364,718 or by pertussis toxin, indicating that gastrin targets the SRE via specific CCK-B receptors through a mechanism independent of Gi. Inhibition of protein kinase C (PKC) either by prolonged (24 h) exposure of the cells to the phorbol ester 12- O-tetradecanoylphorbol 13-acetate (100 nM) or by incubation with the selective inhibitor GF-109203X (3.5 μM) resulted in an 80% reduction in luciferase activity. Similar results were observed in the presence of the specific extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor PD-98059 (50 μM). We measured ERK2 activity in AR42J cells via in-gel kinase assays and observed that gastrin (1 pM-100 nM) induced ERK2 enzyme activity in a dose-dependent manner. Addition of GF-109203X and PD-98059, either alone or in combination, produced, respectively, partial and total inhibition of gastrin-induced ERK2 activity. Gastrin induction of ERK2 activity also resulted in a threefold increase in the transcriptional activity of Elk-1, a factor known to bind to the c- fos SRE and to be phosphorylated and activated by ERK2. PD-98059 blocked the growth-promoting effect of gastrin on the AR42J cells, demonstrating that this effect depends on activation of MEK. Our data lead us to conclude that the trophic actions of gastrin are mediated by ERK2-induced c- fos gene expression via PKC-dependent and -independent pathways.

scholarly journals Long Noncoding RNA HOTAIR Is Associated with Motility, Invasion, and Metastatic Potential of Metastatic Melanoma

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lihua Tang ◽  
Wei Zhang ◽  
Bing Su ◽  
Bo Yu
Keyword(s):  
Lymph Node ◽  
Cell Motility ◽  
Metastatic Melanoma ◽  
Melanoma Cell ◽  
Noncoding Rna ◽  
Primary Melanoma ◽  
Melanoma Metastasis ◽  
Gelatin Matrix ◽  
Gelatinase Activity

Metastatic melanoma, the primary cause of skin cancer-related death, warrants new therapeutic approaches that target the regulatory machinery at molecular level. While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types, limited data are available on the expression and function of lncRNAs in melanoma metastasis. The primary objective of this study was to investigate the role of 6 metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown of HOTAIR resulted in the reduction of motility and invasion of human melanoma cell line A375, as assessed by wound healing assay and Matrigel-based invasion assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR is overexpressed in metastatic tissue, which is associated with the ability of HOTAIR to promote melanoma cell motility and invasion. These data indicate that lncRNAs may be involved in the metastasis of melanoma and provide support for further evaluation of lncRNAs in melanoma.

scholarly journals Exploration and Validation of Metastasis-associated Genes for Skin Cutaneous Melanoma

2021 ◽  
Author(s):  
Hong Luan ◽  
Linge Jian ◽  
Ye He ◽  
Tuo Zhang ◽  
Yanna Su ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cutaneous Melanoma ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Primary Melanoma ◽  
Gene Interaction ◽  
Skin Tumor ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
Hub Gene

Abstract Background: Skin cutaneous melanoma is a malignant and highly metastatic skin tumor, and its morbidity and mortality are still rising worldwide. However, the molecular mechanisms that promote melanoma metastasis are unclear. Methods: Two datasets (GSE15605 and GSE46517) were retrieved to identify the differentially expressed genes (DEGs), including 23 normal skin tissues (N), 77 primary melanoma tissues (T) and 85 metastatic melanoma tissues (M). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to explore the functions of the DEGs. The protein–protein interaction (PPI) network was constructed using the STRING tool and Cytoscape software. We used the cytoHubba plugin of Cytoscape to identify the most significant hub genes by five topological analyses (Degree, Bottleneck, MCC, MNC, and EPC). Hub gene expression was validated using the UALCAN website. Clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Finally, we explored the association between metastasis-associated genes and immune infiltrates through the Tumor Immune Estimation Resource (TIMER) database and performed drug-gene interaction analysis using the Drug-Gene Interaction database.Results: A total of 294 specific genes were related to melanoma metastasis and were mainly involved in the positive regulation of locomotion, mitotic cell cycle process, and epithelial cell differentiation. Four hub genes (CDK1, FOXM1, KIF11, and RFC4) were identified from the cytoHubba plugin of Cytoscape. CDK1 was significantly upregulated in metastatic melanoma compared with primary melanoma, and high expression of CDK1 was positively correlated with poor prognosis. We found that CDK1 expression correlated positively with the infiltration levels of macrophage cells (Rho = -0.164, P = 2.02e-03) and neutrophil cells (Rho = 0.269, P = 2.72e-07) in SKCM metastasis. In addition, we identified that CDK1 had a close interaction with 10 antitumor drugs. Conclusions: CDK1 was identified as a hub gene involved in the progression of melanoma metastasis and may be regarded as a therapeutic target for melanoma patients to improve prognosis and prevent metastasis in the future.

scholarly journals Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Wenkang Luan ◽  
Yuting Ding ◽  
Haolan Xi ◽  
Hongru Ruan ◽  
Feng Lu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Melanoma Cell ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Melanoma Metastasis ◽  
Mesenchymal Transition ◽  
Melanoma Patients

Abstract Background Cancer-secreted exosomal miRNAs regulates the biological processes of many tumours. The serum level of exosomal miR-106b-5p is significantly increased in melanoma patients. However, the role and molecular mechanisms of exosomal miR-106b-5p in melanoma remains unclear. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-106b-5p and EphA4 in melanoma tissues. Transmission electron microscopy (TEM) and western blotting were used to identify exosome. QRT-qPCR and Cy3-labelled miR-106b-5p were used to demonstrated the transmission of melanoma cell-secreted exosomal miR-106b-5p. Western blotting, Immunofluorescence, adhesion, transwell and scratch wound assay were used to explore the role of exosomal miR-106b-5p in melanocytes. Luciferase reporter assays and RNA-Chromatin Immunoprecipitation (ChIP) assay were used to confirm whether erythropoietin-producing hepatocellular carcinoma receptor A4 (EphA4) was a direct target of miR-106b-5p. Results We found that miR-106b-5p levels were increased in melanoma tissue, and high miR-106b-5p expression is an independent risk factor for the overall survival of patients with melanoma. miR-106b-5p is enriched in melanoma cell-secreted exosomes and transferred to melanocytes. Exosomal miR-106b-5p promotes the epithelial-to-mesenchymal transition (EMT), migration, invasion and adhesion of melanocytes. Exosomal miR-106b-5p exerted its role by targeting EphA4 to activate the ERK pathway. We demonstrated that exosomal miR-106b-5p promoted melanoma metastasis in vivo through pulmonary metastasis assay. Conclusions Thus, melanoma cell-secreted exosomal miR-106b-5p may serve as a diagnostic indicator and potential therapeutic target in melanoma patients.

scholarly journals Identification of Metastasis-Associated Gene And Its Correlation With Immune Infiltrates For Skin Cutaneous Melanoma

2021 ◽  
Author(s):  
Hong Luan ◽  
Ye He ◽  
Linge Jian ◽  
Tuo Zhang ◽  
Liping Zhou
Keyword(s):  
Metastatic Melanoma ◽  
Cutaneous Melanoma ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Gene Expression Omnibus ◽  
Skin Tumor ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
P53 Signaling ◽  
Genes Expression

Abstract Background: Skin cutaneous melanoma is a malignant and highly metastatic skin tumor. As the most common cause of death in skin cancer, its morbidity and mortality are still rising worldwide. However, the molecular mechanisms of melanoma metastasis are unclear. Methods: Three Gene Expression Omnibus (GEO) datasets (GSE15605, GSE7553 and GSE8401) were downloaded to identify the differentially expressed genes (DEGs) between primary and metastatic melanoma samples. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to explore the functional of DEGs by Metascape. The protein-protein interaction (PPI) network was constructed using STRING tool and Cytoscape software. We used the cytoHubba plugin of Cytoscape to identify the most significant hub genes by four topological analyses (Degree, MCC, DMNC, and MNC). Hub genes expression was validated using UALCAN website. Finally, we explored the association between metastasis-associated genes and immune infiltrates through Tumor Immune Estimation Resource (TIMER) database.Results: In total, we obtained 196 DEGs including 12 upregulated and 184 downregulated genes. GO and KEGG enrichment results indicated that DEGs were mainly concentrated in epidermis development, cornified envelope, structural molecule activity, and p53 signaling pathway. Eight hub genes were identified to be closely related to melanoma metastasis, including SPRR1B, DSC1, PKP1, TGM1, DSG1, IVL, SPRR1A and DSC3. On the ULCAN website, all hub genes expression levels are lower in metastatic tissues than in primary cancers. Results from TIMER database revealed that DSC1 and TGM1 were significantly related with most of immune cell infiltration.Conclusions: SPRR1B, DSC1, PKP1, TGM1, DSG1, IVL, SPRR1A and DSC3 may be hub genes involved in the progression of melanoma metastasis and thus may be regarded as therapeutic targets in the future. DSC1 and TGM1 play an important role in the microenvironment of metastatic melanoma by regulating the tumor infiltration of immune cells.

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