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Sevoflurane (Sevo) is neuroprotective in ischaemic injury, but its specific mechanism in the disease from microRNA‐203‐3p/histone deacetylases 4/B‐cell lymphoma 2 (miR‐203‐3p/HDAC4/Bcl‐2) axis asks for a comprehensive explanation. A middle cerebral artery occlusion (MCAO) mouse model was established by nylon suture method. miR‐203‐3p and HDAC4 expression was measured in mouse brain tissues. The MCAO mice were exposed to Sevo or injected with miR‐203‐3p‐ or HDAC4‐related plasmids. In response to Sevo treatment or plasmid interference, neurological function, brain pathology, neuronal apoptosis and inflammation were determined. The interactions of miR‐203‐3p and HDAC4, and HDAC4 and Bcl‐2 were verified. MCAO mice presented down‐regulated miR‐203‐3p and up‐regulated HDAC4. Sevo improved neurological function, brain pathological damage and reduced neuronal apoptosis and inflammation in MCAO mice, while overexpressing miR‐203‐3p further enhanced those effects. HDAC4 overexpression antagonized the impacts of miR‐203‐3p up‐regulation on MCAO mice. The targeting relation existed between miR‐203‐3p and HDAC4, as well as between HDAC4 and Bcl‐2. It is clearly elucidated that miR‐203‐3p enhances the protective effects of Sevo on MCAO mice through elevating Bcl‐2 and down‐regulating HDAC4, potentially and clinically offering an effective treatment method with Sevo for cerebral ischaemic injury. [ABSTRACT FROM AUTHOR]

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3′-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Dendritic cell-derived exosomes have been proven to be efficient adjuvant options for anti-tumor vaccines in cancer immunotherapy. However, their potency in atherosclerosis remains unclear. Here we summarize the association of microRNA-203-3p (miR-203-3p) with dendritic cell-derived exosomes and atherosclerosis. Firstly, dendritic cell-derived exosomes and bone marrow-derived macrophages were isolated, after which expression of miR-203-3p and cathepsin S was determined. After the establishment of atherosclerosis mouse models, gain- and loss-of-function experiments were conducted for the analysis of effects of miR-203-3p and cathepsin S on foam-cell formation, lipid accumulation, collagen deposition and serum total cholesterol. The results found high expression of cathepsin S in atherosclerosis mice and downregulation of miR-203-3p in the serum of atherosclerosis patients and ox-LDL-simulated bone marrow-derived macrophages. Cathepsin S was the target gene of miR-203-3p. miR-203-3p transporting from exosomes to bone marrow-derived macrophages resulted in inhibition of cathepsin S expression and atherosclerosis-related phenotypes in bone marrow-derived macrophages, thus alleviating atherosclerosis in mice, and this process was found to involve the p38/MAPK signaling pathway. These findings provided evidence that the transfer of miR-203-3p by dendritic cell-derived exosomes targeted cathepsin S in bone marrow-derived macrophages to attenuate atherosclerosis progression in mice, serving as a promising clinical target for atherosclerosis.