BackgroundPancreatic cancer is a fatal disease with a very poor prognosis due to its characteristic insidious symptoms, early metastasis, and chemoresistance. Circular RNAs (circRNAs) are involved in the development of pancreatic cancer.AimHence, the aim of this study is to elucidate the mechanism of circRNA_000864 in regulating BTG2 expression in pancreatic cancer by binding to miR-361-3p.MethodsCircRNA_000864, miR-361-3p, and BTG2 expression patterns in the pancreatic cancer tissues were detected by RT-qPCR. Correlation among circRNA_000864, miR-361-3p, and BTG2 was evaluated by RNA-pull down assay, RNA Immunoprecipitation assay, and dual-luciferase reporter gene assay. After ectopic expression and depletion experiments, 5-ethynyl-2′-deoxyuridine assay, Transwell assay, and flow cytometry were employed to assess the cell proliferation, migration and invasion, cell cycle, and apoptosis. Xenotransplantation of nude mice was conducted to detect the effects of circRNA_000864, miR-361-3p, and BTG2 on tumor growth.ResultsCircRNA_000864 and BTG2 were poorly expressed, and miR-361-3p was highly expressed in the pancreatic cancer tissues. CircRNA_000864 bound to miR-361-3p could target BTG2. Cell proliferation, migration, and invasion were inhibited, and the cell cycle arrest and apoptosis were stimulated after overexpression of circRNA_000864 or BTG2 or downregulation of miR-361-3p. Overexpression of circRNA_000864 or downregulation of miR-361-3p also decreased the tumor growth in vivo.ConclusionsConjointly, our findings elicited that the overexpression of circRNA_000864 could promote BTG2 expression to inhibit pancreatic cancer development by binding to miR-361-3p, which represents an appealing therapeutic target for the treatment of pancreatic cancer.

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Obesity is a chronic metabolic disease caused by an imbalance between energy intake and expenditure during a long period and is characterized by adipose tissue disfunction and hepatic steatosis. The aim of this study was to investigate the effect of 4-methylesculetin (4-ME), a coumarin derivative, upon adipose microenvironment and hepatic steatosis in mice induced by a high-fat diet (HFD), and to explore potential mechanisms of its beneficial effect on metabolic disorders. HFD-fed mice displayed visceral obesity, insulin resistance, and hepatic lipid accumulation, which was remarkably ameliorated by 4-ME treatment. Meanwhile, 4-ME ameliorated adipocyte hypertrophy, macrophage infiltration, hypoxia, and fibrosis in epididymal adipose tissue, thus improving the adipose tissue microenvironment. Furthermore, 4-ME reversed the increase in CD36, PPAR-γ, SREBP-1, and FASN, and the decrease in CPT-1A, PPAR-α, and Nrf2 translocation into the nucleus in livers of HFD mice and in FFA-incubated hepatocytes. Moreover, the beneficial effects of 4-ME upon lipid deposition and the expression of proteins related to lipid metabolism in FFA-induced LO2 cells were abolished by ML385, a specific Nrf2 inhibitor, indicating that Nrf2 is necessary for 4-ME to reduce hepatic lipid deposition. These findings suggested that 4-ME might be a potential lead compound candidate for preventing obesity and MAFLD.