Project description:This study aimed to elucidate the role of microRNA miR-92a-3p in the pathogenesis of adenomyosis. We focused on understanding how miR-92a-3p in exosomes derived from ectopic lesions influences the behavior of endometrial cells, DRG neurons, and Human Umbilical Vein Endothelial Cells (HUVECs), and its potential as a non-invasive diagnostic biomarker. Our findings revealed that MiR-92a-3p is significantly upregulated in exosomes derived from ectopic lesions of adenomyosis. This upregulation was associated with enhanced migration and invasion capabilities in eutopic endometrial cells, DRG neurons, and HUVECs. Furthermore, the study demonstrated a significant correlation between the levels of MiR-92a-3p in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidates an exosomal signaling process via miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Upregulated miR-92a-3p in biofluid exosomes shows promising non-invasive biomarker potential for diagnosis and monitoring of this disease. Our findings unveil novel targets and tools for improved clinical management.
Project description:Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are central modulators of cellular stress responses, but knowledge about miRNA–mRNA interactions that determine neuronal outcome during inflammation is limited. Here, we combined unbiased neuron-specific miRNA with mRNA sequencing to assemble the regulatory network that mediates robustness against neuroinflammation. As a critical miRNA-network hub we defined miR-92a. Genetic deletion of miR-92a exacerbated the disease course of mice undergoing experimental autoimmune encephalomyelitis (EAE), whereas miR-92a overexpression protected neurons against excitotoxicity. As a key miR-92a target transcript, we identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) that was suppressed in inflamed neurons in mouse EAE and human MS. Accordingly, Cpeb3 deletion improved neuronal resistance to excitotoxicity and ameliorated EAE. Together, we discovered that the miR-92a–Cpeb3 axis confers neuronal robustness against inflammation and serves as potential target for neuroprotective therapies.
Project description:Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are central modulators of cellular stress responses, but knowledge about miRNA–mRNA interactions that determine neuronal outcome during inflammation is limited. Here, we combined unbiased neuron-specific miRNA with mRNA sequencing to assemble the regulatory network that mediates robustness against neuroinflammation. As a critical miRNA-network hub we defined miR-92a. Genetic deletion of miR-92a exacerbated the disease course of mice undergoing experimental autoimmune encephalomyelitis (EAE), whereas miR-92a overexpression protected neurons against excitotoxicity. As a key miR-92a target transcript, we identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) that was suppressed in inflamed neurons in mouse EAE and human MS. Accordingly, Cpeb3 deletion improved neuronal resistance to excitotoxicity and ameliorated EAE. Together, we discovered that the miR-92a–Cpeb3 axis confers neuronal robustness against inflammation and serves as potential target for neuroprotective therapies.
