BMSC-Derived Exosomes Carrying lncRNA-ZFAS1 Alleviate Pulmonary Ischemia/Reperfusion Injury by UPF1-Mediated mRNA Decay of FOXD1.

Bone marrow-derived mesenchymal stem cells (BMSCs) exert protective effects against pulmonary ischemia/reperfusion (I/R) injury; however, the potential mechanism involved in their protective ability remains unclear. Thus, this study aimed to explore the function and underlying mechanism of BMSC-derived exosomal lncRNA-ZFAS1 in pulmonary I/R injury. Pulmonary I/R injury models were established in mice and hypoxia/reoxygenation (H/R)-exposed primary mouse lung microvascular endothelial cells (LMECs). Exosomes were extracted from BMSCs. Target molecule expression was assessed by qRT-PCR and Western blotting. Pathological changes in the lungs, pulmonary edema, apoptosis, pro-inflammatory cytokine levels, SOD, MPO activities, and MDA level were measured. The proliferation, apoptosis, and migration of LMECs were detected by CCK-8, EdU staining, flow cytometry, and scratch assay. Dual-luciferase reporter assay, RNA pull-down, RIP, and ChIP assays were performed to validate the molecular interaction. In the mouse model of pulmonary I/R injury, BMSC-Exos treatment relieved lung pathological injury, reduced lung W/D weight ratio, and restrained apoptosis and inflammation, whereas exosomal ZFAS1 silencing abolished these beneficial effects. In addition, the proliferation, migration inhibition, apoptosis, and inflammation in H/R-exposed LMECs were repressed by BMSC-derived exosomal ZFAS1. Mechanistically, ZFAS1 contributed to FOXD1 mRNA decay via interaction with UPF1, thereby leading to Gal-3 inactivation. Furthermore, FOXD1 depletion strengthened the weakened protective effect of ZFAS1-silenced BMSC-Exos on pulmonary I/R injury. ZFAS1 delivered by BMSC-Exos results in FOXD1 mRNA decay and subsequent Gal-3 inactivation via direct interaction with UPF1, thereby attenuating pulmonary I/R injury.

Sevoflurane Inhibits Glioma Cells Proliferation and Metastasis through miRNA-124-3p/ROCK1 Axis.

Malignant glioma is the most common primary malignancy in the brain. It is aggressive, highly invasive, and destructive. Studies have shown that sevoflurane can affect the invasion and migration of a variety of malignant tumors. However, its effects on human glioma cells and related mechanisms are not clear. Cultured U251 and U87 cells were pretreated with sevoflurane. The effect of sevoflurane on cell proliferation, migration, apoptosis and invasion ability were evaluated by MTT, wound healing assay, cell apoptosis and transwell assays, respectively. miRNA-124-3p and ROCK1 signaling pathway genes expression in sevoflurane treated cell lines was measured by quantitative real-time PCR (qRT-PCR) and western blotting analysis. The potential target genes of miRNA were predicted by online software. Luciferase reporter assay was employed to validate the direct targeting of ROCK1 by miRNA-124-3p. In present studies, sevoflurane inhibits glioma cells proliferation, invasion and migration. Additionally, inversely correlation between miR-124-3p and ROCK1 expression in sevoflurane treated glioma cells was observed. Furthermore, sevoflurane inhibits glioma cells proliferation, migration and invasion through miR-124-3p/ROCK1 axis. Taken together, our study revealed that sevoflurane can inhibit glioma cell proliferation, invasion and migration. Its mechanism may be related to the upregulation of miR-124-3p, which suppresses ROCK1 signaling pathway. The results of the study will help to understand the pharmacological effects of inhaled general anesthetics more comprehensively and help to provide an experimental basis for selecting more reasonable anesthetics for cancer patients.