SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression.

Exosomes are membrane-derived vesicles and play a critical role in cell signaling by transferring RNAs and proteins to target cells through fusion with the cell membrane. Long non-coding RNA-small nucleolar RNA host gene 9 (lncRNA-SNHG9) was proven to be an important element in lncRNA-mRNA interaction networks during adipocyte differentiation, suggesting its potential involvement in the development of obesity, an important risk factor of cardiovascular and cerebrovascular endothelial dysfunction. However, the role of lncRNA-SNHG9 within the exosome in endothelial dysfunction of obese patients is largely unknown. In this study, we proved that adipocytes-derived exosomal SNHG9 were downregulated in obese persons and further decreased in obese individuals with endothelial dysfunction. Functional experimentations demonstrated that adipocytes-derived exosomal SNHG9 alleviated inflammation and apoptosis in endothelial cells. Bioinformatic analysis revealed that there was a potential interaction between SNHG9 and the TNF receptor type 1-associated death domain protein (TRADD) mRNA. Then, RNA-binding protein immunoprecipitation assay based on Ago2 antibody and ribonuclease protection assay demonstrated that exosomal SNHG9 directly bound to a specific region in TRADD mRNA sequence and formed an RNA dimeric inducible silencing complex. Moreover, knockdown of TRADD markedly inhibited inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs), whereas overexpression of TRADD dramatically neutralized the protective effect of exosomal SNHG9 on epithelial dysfunction. Therefore, SNHG9 could prevent endothelial dysfunction in obese patients by suppressing inflammation and apoptosis, indicating that SNHG9 may be a potential therapeutic target for obese patients with endothelial dysfunction.

Inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis through regulation of Notch signaling.

Cardiomyocyte apoptosis contributes to the pathological process of ischemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathological process of myocardial infarction by regulating cardiomyocyte apoptosis. Previous studies have reported that miR-363 is an apoptosis-related miRNA. However, whether miR-363 is involved in regulating cardiomyocyte apoptosis remains unclear. This study aimed to investigate the potential role of miR-363 in the regulation of hypoxia-induced cardiomyocyte apoptosis. We found that miR-363 expression was significantly increased in hypoxic cardiomyocytes and that inhibition of miR-363 effectively protected cardiomyocytes against hypoxia-induced apoptosis. Bioinformatics analysis predicted that Notch1 is a potential target gene of miR-363. This finding was validated by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. miR-363 inhibition significantly promoted the activation of Notch signaling in hypoxic cardiomyocytes. However, knockdown of Notch1 markedly reversed the protective effects induced by miR-363 inhibition. Furthermore, blocking the Notch signaling also significantly abrogated the protective effects of miR-363 inhibition. Overall, these findings suggest that inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis through promotion of Notch1 expression and activation of Notch signaling. Our study provides a novel understanding of the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a potential therapeutic target for myocardial infarction.

Lack of association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms and lymphoid malignancy risk: evidence from a meta-analysis.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms have been associated with susceptibility to lymphoid malignancies. However, results from the published single studies are inconsistent. Therefore, the present meta-analysis was conducted to get a more accurate estimation of the relationship between CTLA-4 gene polymorphisms and the lymphoid malignancy risk. We identified nine independent studies accounting for 3090 subjects up to January 30, 2016. Summary odds ratios (OR) and 95 % confidence intervals (CI) were used to evaluate the risk of lymphoid malignancies. Overall, no significant association was found between +49A/G (rs231775), -318C/T (rs5742909), and +6230A/G (rs3087243) CTLA-4 gene polymorphisms and lymphoid malignancies. Furthermore, ethnicity (Asian and Caucasian) and histopathology subgroup analyses (non-Hodgkin's lymphoma) also failed to detect an association between the studied polymorphisms and lymphoid malignancy risk. Our study shows that common CTLA-4 gene polymorphisms may not contribute to lymphoid malignancy susceptibility based on the current evidence.