MLPH regulates EMT in pancreatic adenocarcinoma through the PI3K-AKT signaling pathway.

Pancreatic adenocarcinoma (PAAD) is an extremely malignant tumor, and most patients develop postoperative metastases. Melanophilin (MLPH) is involved in the progression of various tumors, but its molecular mechanisms and role in pancreatic cancer progression are unknown. In this study, differential MLPH expression in cancer tissues and the adjacent tissues was evaluated using the Gene Expression Profiling Interaction Analysis 2 (GEPIA 2) and Human Protein Atlas (HPA) databases. The role of MLPH in PAAD proliferation, invasion, and migration in vitro was explored via clone formation, Cell Counting Kit-8 assay, Transwell assay, and western blot. The in vivo validation of function was performed using a metastatic nude mouse model. The result showed that the pancreatic cancer tissues had significantly higher MLPH expression levels than the noncancerous pancreatic tissues. MLPH expression changes were related to PAAD cell proliferation, invasion, and migration. The western blotting demonstrated that PAAD cells had reduced Epithelial-mesenchymal transition (EMT)-related marker expression. Furthermore, overexpressing MLPH enhanced cell proliferation, migration, and invasion, and increased EMT-related marker expression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the molecular mechanism underlying the effect of MLPH on PAAD was significantly related to the PI3K-AKT pathway. LY294002 blocked the MLPH overexpression-mediated enhanced cell invasion and migration and inhibited EMT-associated marker expression. Conversely, 740Y-P reversed the inhibitory effects of MLPH downregulation and led to cell migration, invasion, and EMT. MLPH regulated EMT to mediate PAAD cell invasive migration through the PI3K-AKT pathway. The results indicated that MLPH is a possible target for blocking PAAD metastasis.

FUT11 expression in gastric cancer: its prognostic significance and role in immune regulation.

BACKGROUND: Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the key enzyme is fucosyltransferase (FUT). FUT11 is a member of the fucosyltransferase family and has been closely associated with the development of multiple cancers. However, the specific relationship between FUT11 and GC prognosis and its molecular mechanism has not been fully studied. This study explored FUT11 expression, clinical correlation, and its role in GC occurrence and development to deepen understanding of its function. METHODS: FUT11 expression in 33 cancers was preliminarily analyzed using the Tumor Immunoassay Resource (TIMER2.0) database. FUT11 expression in GC was evaluated using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and Gene Expression Profiling Interactive Analysis (GEPIA2) data and verified using the Gene Expression Omnibus (GEO) GSE65801 dataset. Furthermore, we studied the survival prognosis of FUT11 in GC and analyzed its effect on the survival rate of patients with GC using the KM-plotter. We also performed COX regression analysis on TCGA GC clinical data and analyzed FUT11 expression in the pathway using the STRING and LinkedOmics databases. Moreover, the relationship between FUT11 and GC immune infiltration level was examined, and the Kaplan-Meier survival analysis diagram was constructed. The FUT11 genetic variation information was retrieved using cBioPortal, and its drug sensitivity was analyzed using CellMiner. Finally, differential FUT11 expression in GC tissues was verified using immunohistochemistry. RESULTS: The data mining and analysis demonstrated that FUT11 expression was abnormally elevated in GC tissues and correlated with poor patient prognosis. The FUT11 expression level was an independent prognostic factor for GC. The difference in FUT11 expression level resulted in different degrees of immune cell infiltration in the patients with GC, which might regulate the tumor microenvironment. FUT11 affected GC development by participating in cancer pathways such as PI3K-AKT, neuroactive ligand-receptor, and MAPK. Immunohistochemical staining revealed that FUT11 was highly expressed in GC. CONCLUSIONS: This study revealed that FUT11 expression is significantly increased in GC tissues. This increase is associated with poor prognosis and might affect immune regulation. FUT11 might have immunological and targeted therapeutic value, providing a new approach to GC treatment.

ITGA11, a Prognostic Factor Associated with Immunity in Gastric Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear. Methods: The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry. Results: The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib. Conclusion: The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.

Influence of selenium and fluoride on blood antioxidant capacity of rats.

This study is to explore the effect of selenium and fluoride on blood antioxidant capacity of rats, and try to find out the optimal level of selenium in drinking water against fluorosis. Animals were divided into control group, sodium fluoride treated group (NaF, 50 mg/L) and selenium+NaF treated group (sodium selenite 0.375, 0.75, 1.5 mg/L) in water were respectively administered to male rats, which were decapitated after 6 months. Their blood was collected for GSH-Px activity, plasma SOD activity, T-AOC assay, uric acid assay, sialic acid (SA) content and MDA content, and the fluidity of erythrocyte membrane by electron spin resonance (ESR) was analyzed. The results showed that, compared with the control group, the blood antioxidant capacity of the rats exposed to fluoride was down-regulated significantly (P<0.05, P<0.01), MDA content increased significantly (P<0.05), the fluidity of erythrocyte membrane decreased (P<0.05, P<0.01). Meanwhile, the treatments of selenium along with NaF compared with fluorosis group, SOD activity, GSH-Px activity and T-AOC assay increased respectively, MDA content decreased significantly (P<0.05) in NaF+Se (Se 0.75, 1.5 mg/L) treated groups, uric acid level was up-regulated, but had no statistical significant difference (P>0.05). The fluidity of erythrocyte membrane showed significant increase (P<0.05), the content of SA was lower. Fluorosis could induce the decline of blood antioxidant capacity and the fluidity of erythrocyte membrane, as evident in this study, and Se at different levels possess some antagonistic effects on blood induced by fluoride. However, high dose of selenium (1.5 mg/L) is the optimum concentration.

Intervention of selenium on chronic fluorosis-induced injury of blood antioxidant capacity in rats.

This study was conducted to further explore the effects of selenium on the blood antioxidant capacity in rats exposed to fluoride to find out the optimal dosage level of selenium. Animals were divided into prevention sequence (Selenium → NaF, water → NaF) and treatment sequence (NaF → Selenium, NaF → water) (sodium fluoride 50 mg/L; sodium selenite 0.375, 0.75, 1.5 mg/L). The exposure time was 12 months. Then, the fluidity of erythrocyte membrane by electron spin resonance was analyzed, and the blood was collected for GSH-Px and SOD activity, total antioxidant capacity (T-AOC) and uric acid assay, sialic acid and MDA content. The results showed that, compared with control group, GSH-Px activity and T-AOC level increased significantly (P < 0.05), and SOD activity was raised in varying degrees in prevention and treatment groups, respectively. Uric acid level was up-regulated, but no significant differences were observed (P > 0.05). The fluidity of erythrocyte membrane showed significant increase (P < 0.05). As evident in this study, when the dose of selenium was 0.75 mg/L, all the activities of antioxidant enzymes increased significantly in prevention sequence; but in treatment sequence, the optimum intervention concentration was 1.5 mg/L. On the basis of results, the preventive effect of selenium was superior to treatment effect on the oxidative stress induced by an overdose of fluoride.