miR‐488 mediates negative regulation of the AKT/NF‐κB pathway by targeting Rac1 in LPS‐induced inflammation

Abstract

Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases.However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B κ-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-κB) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3′-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-κB was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells. K E Y W O R D SAKT/NF-κB, endometritis, lipopolysaccharide, miR-488, ROS

MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)

“…Previous studies have shown that miR-488 affects the pathophysiological processes of various diseases. [35][36][37] In this study, it was found that over-expression of miR-488-3p inhibited neuron apoptosis and alleviated cerebral infarction caused by ischemic stroke in mice, indicating that miR-488-3p might be a potential curative target for ischemic stroke. Previous studies have shown that VPS4 affects extracellular secretion and lysosomal and cell proliferation and differentiation through regulating specific signaling pathways.…”

“…Some researchers have provided data showing that miR-488 expression is negatively regulated by inhibiting ROS and AKT/NF κB pathways in LPSinduced inflammation of intimal epithelial cells. 35 In osteosarcoma (OS) cells, miR-488 is down-regulated by targeting aquaporin 3 (AQP3) to inhibit cell proliferation and invasion, 37 indicating that miR-488 is a miRNA of tumor suppressor. Besides, miR-488 participates in drug tolerance of anti-cancer drug cisplatin mediated by eukaryotic translation initiation factor 3a (eIF3a) in non-small cell lung cancer cells (NSCLC).…”

miR-181d/RBP2/NF-κB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis

“…Recent studies have shown that miRNAs play important roles in inflammation and cancer by regulating the NF-κB pathway ( 38 , 39 ). Nevertheless, whether miRNAs could be reversely regulated by NF-κB is largely unknown.…”

miR-181d/RBP2/NF-κB p65 Feedback Loop Promotes Chronic Myeloid Leukemia Blast Crisis

“…Recent studies have shown that miRNAs play important roles in in ammation and cancer by regulating the NF-κB pathway [33][34][35][36]. Nevertheless, whether miRNAs could be reversely regulated by NF-κB is largely unknown.…”