miR-188-5p silencing improves cerebral ischemia/reperfusion injury by targeting Lin28a

• Published in: Metabolic brain disease Vol. 38; no. 7; pp. 2327 - 2338
• Main Authors: Hou, Dan, Pei, Chaoying, Yu, Dan, Yang, Guoshuai
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2023; Springer Nature B.V
• Subjects: Apoptosis; BAX protein; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Biomedicine; Caspase-3; Cerebral infarction; Cytokines; Edema; IL-1β; Inflammation; Injuries; Interleukin 6; Ischemia; Metabolic Diseases; Neurology; Neurosciences; Oncology; Original Article; Reperfusion; Tumor necrosis factor-α; Lin28a; miR-188-5p; Ischemia/reperfusion injury; Ischemic stroke
• ISSN: 0885-7490; 1573-7365; 1573-7365
• DOI: 10.1007/s11011-023-01273-9

This report aimed to explore whether miR-188-5p regulated the pathological regulatory network of cerebral ischemia/reperfusion (I/R) injury. We simulated the cerebral I/R injury model with MACO/R and OGD/R treatments. Neuronal viability and apoptosis were assessed. The contents of miR-188-5p and Lin 28a were evaluated. The abundances of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured. The interaction of miR-188-5p and Lin28a was confirmed. Lin28a silencing was supplemented to determine the delicate regulation of miR-188-5p. We revealed that miR-188-5p was upregulated and Lin28a was downregulated in I/R rats and OGD/R-induced cells. miR-188-5p silencing remarkably reduced the cerebral infarction volume, neurobehavioral score, brain edema, and Evans blue leakage. miR-188-5p silencing enhanced neuronal viability and alleviated apoptosis. The abundance of Bax and cleaved caspase-3 was reduced by miR-188-5p silencing, while Bcl-2 was augmented. miR-188-5p silencing impeded the contents of TNF-α, IL-1β, and IL-6. miR-188-5p interacted with Lin28a and negatively regulated its expression. Interestingly, extra Lin28a silencing reversed apoptosis and the content of inflammatory cytokines. Our studies confirmed that miR-188-5p silencing alleviated neuronal apoptosis and inflammation by mediating the expression of Lin28a. The crosstalk of miR-188-5p and Lin28a offered a different direction for ischemic stroke therapy.