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The present study aimed to explore the expression and effects of microRNA (miR)-155 in synovial fibroblasts of patients with rheumatoid arthritis (RA). A total of 89 synovial tissues from RA patients and 49 control synovial tissues were collected, and the levels of miR-155 were measured by reverse transcription quantitative-PCR and western blotting. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues from the control group and were used to evaluate the roles of miR-155 and forkhead box protein O3a (FOXO3a). MTT assay was used to measure the proliferation of FLS. The expression of miR-155 in RA synovial tissues was significantly higher than that in the control group, but the expression of FOXO3a was significantly lower. In RA synovial tissues, miR-155 expression was negatively correlated with FOXO3a expression, but was positively correlated with the release of inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). A dual-luciferase reporter system showed that miR-155 inhibited the expression of FOXO3a in FLS cells. miR-155 also promoted secretion of the inflammatory cytokines IL-1β, IL-6 and TNF-α by FLS and proliferation of these cells by targeting FOXO3a.

Purpose Angiogenesis is required for improving myocardial function and is a key factor in long-term prognosis after an acute myocardial infarction (AMI). Although exosomes are known to play a crucial role in angiogenesis, the role of peripheral exosomes in angiogenic signal transduction in patients with AMI remains unclear. Here, we explored the effect of exosomes extracted from the peripheral serum of AMI patients on angiogenesis and elucidated the downstream pathways. Patients and Methods Serum exosomes were obtained from patients with AMI (AMI-Exo) and healthy individuals (Con-Exo). The exosomes were cocultured with human umbilical vein endothelial cells (HUVECs) in vitro, with aortic rings ex vivo, and were used to treat mouse hind-limb ischemia and mouse AMI model in vivo. Results AMI-Exo raised HUVEC proliferation, tube formation, and migration, and enhanced microvessel sprouting from aortic rings compared to Con-Exo, both in vitro and ex vivo. Quantitative reverse transcription-polymerase chain reaction revealed that the abundance of miR-126-3p, a crucial regulator of angiogenesis, was increased in AMI-Exo. The inhibition of miR-126-3p decreased the benefits of AMI-Exo treatment, and miR-126-3p upregulation enhanced the benefits of Con-Exo treatment in HUVECs, aortic rings, the mouse hind-limb ischemia model, and the mouse AMI model. Knockdown and overexpression analyses revealed that miR-126-3p regulated angiogenesis in HUVECs by directly targeting tuberous sclerosis complex 1 (TSC1). Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1α and VEGFA expression, ultimately promoting angiogenesis. Conclusion Collectively, our results provide a novel understanding of the function of exosomes in angiogenesis post AMI. We demonstrated that exosomes from the peripheral serum of AMI patients promote angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α signaling pathway.

BackgroundHepatocellular carcinoma (HCC) is the fifth most common malignancy in China, and China’s annual number of new cases accounts for about 45% of the world total. This research was aimed to study the expression of TBX3 protein in HCC and exploring its clinical significance.Material/MethodsWe collected tumor tissues and adjacent non-tumoral tissues of 174 patients with HCC undergoing surgical resection. The expression of TBX3 protein in different tissues and cell lines in vitro (LO2, HHL-5, MHC97-L, MHC97-H) was detected by immunohistochemistry or Western blotting, and the relationship between TBX3 expression and clinical data of patients with HCC was analyzed.ResultsThe expression of TBX3 protein in HCC was significantly correlated with histological grade, tumor size, cancer cell metastasis, hepatitis B surface antigen, and the expression of Ki-67 in tumor tissues (P<0.05), and it was positively correlated with serum AFP level (r=0.766, P<0.05). The expression of TBX3 increased with increased histological grade in HCC (P<0.05). Cox regression analysis showed that the expression of TBX3 protein in HCC was an independent risk factor for prognosis (OR=0.524, 95% CI=0.283–0.964). The 5-year survival rate of patients with HCC that highly expressed TBX3 protein was 20.83%, which was significantly lower than the 40.20% rate in patients with low expression (P<0.05).ConclusionsThe expression of TBX3 in HCC patients undergoing surgical resection is high, and its expression increases with the degree of tumor differentiation. It is related to the metastasis of tumor cells and is positively correlated with the serum level of AFP and may affect the survival time of HCC patients undergoing surgical resection.