Long Noncoding RNA SAMMSON Promotes Melanoma Progression by Inhibiting FOXA2 Expression.

Long noncoding RNAs (lncRNAs) play crucial roles in melanoma initiation and development, serving as potential therapeutic targets and prognostic markers for melanoma. lncRNA survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON) is upregulated in many types of human cancers. However, the functions of SAMMSON in melanoma have not been fully elucidated. This study is aimed at investigating the expression and functions of SAMMSON in melanoma development. Bioinformatics analysis was performed to determine the expression of SAMMSON and its correlation with the 10-year overall survival (OS) in melanoma patients. Cell proliferation, migration, invasion, and tumorigenesis were detected by MTT, colony formation, Transwell assays, and mouse xenograft model. The expression of cell cycle-related factors, epithelial-to-mesenchymal transition (EMT) makers, and matrix metalloproteinases (MMPs) was assessed by RT-qPCR and western blotting analysis. The results demonstrated that SAMMSON expression was upregulated in melanoma tissues and cells, and lower SAMMSON expression was correlated with longer 10-year OS. SAMMSON knockdown decreased the proliferation, migration, and invasion of melanoma cells by regulating the expression of proliferation-related genes, EMT factors, and MMPs, respectively. Additionally, Forkhead box protein A2 (FOXA2) was confirmed to be a target of SAMMSON, and the biological effects induced by FOXA2 overexpression were similar to those induced by SAMMSON silencing in melanoma cells. Further studies showed that SAMMSON downregulated FOXA2 expression in melanoma cells by modulating the EZH2/H3K27me3 axis. Taken together, our data indicate that SAMMSON plays an important role in melanoma progression and can be a valuable biomarker and therapeutic target in melanoma.

Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway.

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-ß (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.

NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma.

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is the first enzyme in the de novo purine nucleotide synthesis pathway and is essential for cell development. However, the effect of PRPS1 on melanoma proliferation and metastasis remains unclear. This study aimed to investigate the regulatory mechanism of PRPS1 in the malignant progression of melanoma. Here, we found PRPS1 was upregulated in melanoma and melanoma cells. In addition, our data indicated that PRPS1 could promote the proliferation and migration and invasion of melanoma both in vitro and in vivo. PRPS1 also could inhibit melanoma cell apoptosis. Furthermore, we found NRF2 is an upstream transcription factor of PRPS1 that drive malignant progression of melanoma.

LINC00511 as a prognostic biomarker for human cancers: a systematic review and meta-analysis.

BACKGROUND: Long intergenic non-coding RNA 00511 (LINC00511) is highly expressed in diverse cancers and has a correlation with poor clinical outcomes for cancer patients. In view of contradictory data among published data, we aim to evaluate the prognostic role of LINC00511 for cancer patients. METHODS: In the present study, a meta-analysis of related studies has been performed to investigate the prognostic significance of LINC00511 in cancer patients. Relevant studies published before December 22, 2019 were systematically searched online in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. The relationship between LINC00511 expression and cancer patients' survival, including overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS) and progression-free survival (PFS), was evaluated using pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). The association between LINC00511 expression and clinicopathological features was assessed using odd ratios (ORs) and their corresponding 95% CIs. RESULTS: A total of 14 eligible studies with 1883 patients were enrolled in the present meta-analysis. The results demonstrated that elevated expression of LINC00511 was significantly associated with poor OS (HR = 2.62; 95% CI: 2.00-3.45; p <  0.001), PFS (HR = 1.80; 95% CI: 1.29-2.51; p = 0.001) and DFS/RFS (HR = 2.90; 95% CI: 1.04-8.12; p = 0.04). Additionally, High LINC00511 expression was associated with large tumor size (OR = 3.10; 95% CI: 1.97-4.86; p <  0.00001), lymph node metastasis (OR = 3.11; 95% CI: 2.30-4.21; p <  0.00001), advanced clinical stage (OR = 3.95; 95% CI: 2.68-5.81; p <  0.00001), distant metastasis (OR = 2.39; 95% CI: 1.16-4.93; p = 0.02), and disease recurrence (OR = 4.62; 95% CI: 2.47-8.65; p <  0.00001). Meanwhile, no correlation was found between LINC00511 expression and age, gender, and histological grade. These findings were consolidated by the results of bioinformatics analysis. CONCLUSIONS: Based on our findings, LINC00511 may serve as a novel prognostic biomarker for cancer patients.

Association between diabetes mellitus and lung cancer: Meta-analysis.

BACKGROUND: This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. MATERIALS AND METHODS: We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. RESULTS: The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. CONCLUSIONS: This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.