ABSTRACT
The prevalence of abnormal glucose and lipid metabolism and its relevant diseases has increased year by year, and it has become a problem that threatens human health. Therefore, finding a more effective way to prevent and treat diseases related to abnormal glucose and lipid metabolism has become an urgent public problem. Agmatine is a polyamine substance which widely presents in mammals.It is a metabolite produced by decarboxylation of L-arginine under the action of arginine decarboxylase, hence also known as decarboxylated arginine. Its biological effects have been confirmed. Previous studies have shown that agmatine possesses anti-diabetic effects in diabetic animals. Agmatine not only increases the insulin secretion form ß-pancreatic cells to inhibit the hyperglycemia, but also attenuates insulin resistance in rats. Agmatine also plays a positive role in lipid metabolism disorders and related diseases by modulating lipid metabolism and fatty acid oxidation.
Subject(s)
Agmatine , Agmatine/pharmacology , Animals , Arginine/metabolism , Glycolipids , Lipid Metabolism , RatsABSTRACT
Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN, COL1A1, COL4A1, COL5A2, NOX4, SPARC, HEYL, SPP1, TIMP1, CTHRC1, TREM2, SFRP4, FBXO32, GPX3, KIF4A, and MMP9 genes associated with GC. The EMT-related pathway was the most significantly altered pathway. TREM2 expression was higher in GC cell lines and was remarkably associated with tumor invasion depth, TNM stage, histological grade, histological type, anatomic subdivision, and Helicobacter pylori state. Knockdown of TREM2 expression inhibited the proliferation, migration, and invasion of GC cells as well as the progression of EMT by PI3K/AKT signaling in vitro. In addition, lung metastasis were decreased in vivo. Conclusions: We identified some important genes associated with the progression of GC via public database analysis, explored and verified the effects of proto-oncogene TREM2 on EMT via the PI3K/AKT pathway. TREM2 may be a novel target in the GC therapy.
ABSTRACT
Lactate dehydrogenase A (LDH-A) is a key enzyme during glycolysis, which increases the synthesis of related proteins and has elevated activity in cancer cells. The role of LDH-A in lung adenocarcinoma (LUAD) progression was investigated in the present study. Expression levels of LDH-A were assessed in LUAD samples, and the relationship between LDH-A expression status and the prognosis of LUAD patients was confirmed. The effect of LDH-A on proliferation, invasion, migration, and colony formation of cancer cells was assessed. We further determined the role of LDH-A in tumor growth in vivo by using xenograft LUAD tumor models. The potential mechanism of LDH-A promotion in LUAD progression was explored. LDH-A showed an abnormally high expression in LUAD, which is closely associated with poor prognosis in patients with LUAD. In in vitro experiments, silencing LDH-A expression in LUAD cells could effectively inhibit proliferation, invasion, migration, and colony formation of cancer cells. In in vivo experiments, tumor growth was markedly inhibited by LDH-A silencing in a xenograft model of LUAD. Notably, LDH-A could also promote tumor progression by regulating epithelial-mesenchymal transition (EMT)-related molecules. LDH-A can promote the malignant biological behaviors of LUAD cells, and thus can be a potential target for LUAD treatment.