Background: Necroptosis has been identified recently as a newly recognized programmed cell death that has an impact on tumor progression and prognosis, although the necroptosis-related gene (NRGs) potential prognostic value in skin cutaneous melanoma (SKCM) has not been identified. The aim of this study was to construct a prognostic model of SKCM through NRGs in order to help SKCM patients obtain precise clinical treatment strategies.Methods: RNA sequencing data collected from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed and prognostic NRGs in SKCM. Depending on 10 NRGs via the univariate Cox regression analysis usage and LASSO algorithm, the prognostic risk model had been built. It was further validated by the Gene Expression Omnibus (GEO) database. The prognostic model performance had been assessed using receiver operating characteristic (ROC) curves. We evaluated the predictive power of the prognostic model for tumor microenvironment (TME) and immunotherapy response.Results: We constructed a prognostic model based on 10 NRGs (FASLG, TLR3, ZBP1, TNFRSF1B, USP22, PLK1, GATA3, EGFR, TARDBP, and TNFRSF21) and classified patients into two high- and low-risk groups based on risk scores. The risk score was considered a predictive factor in the two risk groups regarding the Cox regression analysis. A predictive nomogram had been built for providing a more beneficial prognostic indicator for the clinic. Functional enrichment analysis showed significant enrichment of immune-related signaling pathways, a higher degree of immune cell infiltration in the low-risk group than in the high-risk group, a negative correlation between risk scores and most immune checkpoint inhibitors (ICIs), anticancer immunity steps, and a more sensitive response to immunotherapy in the low-risk group.Conclusions: This risk score signature could be applied to assess the prognosis and classify low- and high-risk SKCM patients and help make the immunotherapeutic strategy decision.

Background: Cutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment. Methods: We downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high-and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy. Results: By correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan-Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature. Conclusion:The 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy.

Introduction. In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity.Material and methods. Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 μmol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 μg/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA),xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot.Results. Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up-regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 μg/mL APS. Conclusions.Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.

BackgroundColon cancer (CC) is a common tumor, but its pathogenesis is still not well understood. Competitive endogenous RNA (ceRNA) theory, ferroptosis and tumor immune infiltration may be the mechanisms of the development of cancer. The purpose of the study is to seek genes connected with both immunity and ferroptosis, and provide important molecular basis for early noninvasive diagnosis and immunotherapy of CC.MethodsWe extracted messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) data of CC from The Cancer Genome Atlas database (TCGA), identified the differentially expressed mRNA (DEmRNA), miRNA (DEmiRNA) and lncRNA (DElncRNA), then constructed a ceRNA network. Venn overlap analysis was used to identify genes associated with immunity and ferroptosis in ceRNA network. The expression and prognosis of target genes were analyzed via Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan database, and we analysed the related functions and signaling pathways of target genes by enrichment analysis. The correlation between target genes and tumor immune infiltrating was explored by CIBERSORT and spearman correlation analysis. Finally, the expression of target genes was detected via quantitative reverse transcription-PCR (qRT-PCR) in CC and normal colon tissues.ResultsResults showed that there were 4 DElncRNA, 4 DEmiRNA and 126 DEmRNA in ceRNA network. NADPH oxidase 4 protein (NOX4) was a DEmRNA associated with immunity and ferroptosis in ceRNA network. NOX4 was highly expressed in CC and connected with unfavourable prognosis. NOX4 was obviously enriched in pathways connected with carcinogenesis and significantly correlated with six kinds of immune cells. Immune checkpoints and NOX4 spearman correlation analysis showed that the expression of NOX4 was positively related to programmed cell death protein 1 (PD-1)-PDCD1, programmed cell death-Ligand 1 (PD-L1)-CD274 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4).ConclusionsTo conclude, our study suggests that NOX4 is associated with both ferroptosis and tumor immunity, and might be a biomarker associated with the carcinogenesis, prognosis of CC and a potential target of CC immunotherapy.

Purpose Cancer seriously endangers human health in every country of the world. New evidence shows that small nucleolar RNAs play important roles in tumorigenesis. Herein, we created this evidence map to systematically assess the impact of dysregulated snoRNAs on cancers. Methods We searched four databases to February 2022 using the keywords, “carcinoma”, “neoplasms”, “tumor”, “cancer”, “snoRNA”, and “small nucleolar rna”. The research data were independently screened by two reviewers. Bubble plot, mind map, heatmap were used to depict the relationship between snoRNAs and cancers. Results In total, 102 studies met the inclusion criteria and were analyzed in this evidence map. In this study, we found that dysregulated snoRNAs were statistically associated with the clinicopathological characteristics of cancer patients, and affected tumor cell phenotypes. Abnormally expressed snoRNAs were associated with poor survival in cancer patients. Current research confirmed that snoRNAs have good diagnostic efficiency for cancers. snoRNAs could modulate biological processes and signaling pathways of different cancer cells by altering rRNA, regulating mRNA, and recruiting protein factors. Conclusion Taken all together, ectopic snoRNAs may serve as new biomarkers for clinical assessment, diagnostic, prognostic prediction of cancer patients, and provide a potential therapeutic strategy for cancer treatment. This article provided a visual analysis of existing evidence on snoRNAs and cancers, which can offer useful information for different researchers interested in snoRNAs.