Downregulated miRNA-324-5p aggravates neuronal injury induced by oxygen-glucose deprivation via modulating RAN

Abstract

Differentially expressed miRNAs in the GEO profile of ischemic stroke were analyzed to clarify the specific role of microRNA-324-5p (miRNA-324-5p) in ischemic stroke and the potential mechanism. After screening out miRNA-324-5p, its level in peripheral blood of stroke patients and in vitro oxygen-glucose deprivation (OGD)-induced primary rat neurons was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of miRNA-324-5p on viability, and apoptosis of OGD-induced neurons were evaluated by CCK-8 and Annexin V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining, respectively. Glucose uptake and caspase-3 activity in OGD-induced neurons transfected with miRNA-324-5p mimics or inhibitor were also examined. The binding of miRNA-324-5p to its target gene RAN was analyzed by dual-luciferase reporter gene assay and western blot analysis. By analyzing the data of GSE46266 profile, miRNA-324-5p expression was shown markedly lower in MCAO rats relative to controls. Identically, we also observed the downregulated miRNA-324-5p in peripheral blood of stroke patients and in vitro OGD-induced primary neurons. Overexpression of miRNA-324-5p accelerated viability, induced apoptosis and strengthened glucose uptake ability of OGD-induced neurons. Knockdown of miRNA-324-5p, conversely, obtained the opposite results. Furthermore, we confirmed the binding of miRNA-324-5p to RAN, the target gene that was negatively regulated by miRNA-324-5p. Importantly, RAN overexpression partially reversed the regulatory effect of miRNA-324-5p on viability and glucose uptake of OGD-induced neurons. miRNA-324-5p is downregulated after ischemic stroke, which aggravates the disease condition by inhibiting neuronal proliferation and glucose uptake via upregulating RAN.

LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis

“…We primarily identified that Ran could be targeted by miR-324-5p, which was consistent with previous study. 43 Small GTPase Ran was a carcinogenic protein. Several miRNAs, including miR-802, miR-2, miR-197, miR-203 could directly bind to Ran to modulate cancer cell behaviors in cancers, 15 , 44–47 which indicated that Ran involved in the regulation of malignant behaviors in cancers.…”

SDSS ameliorates cerebral ischemia/reperfusion injury by inhibiting CLIC4/NLRP3 inflammasome-mediated endothelial cell pyroptosis

“…However, it is important to note that thrombolysis has a strict time window limitation [4]. Once it is exceeded, regaining blood ow can worsen brain injury, known as cerebral ischemia-reperfusion injury (CIRI) [5].…”

“…Stroke is classi ed clinically as ischemic or hemorrhagic, with 80% occurring as ischemic strokes [2]. At present, thrombolysis and mechanical thrombectomy are well established treatments of acute ischemic stroke [3].However, it is important to note that thrombolysis has a strict time window limitation [4]. Once it is exceeded, regaining blood ow can worsen brain injury, known as cerebral ischemia-reperfusion injury (CIRI) [5].…”

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways

“…With regard to miR-324-5p, which we show to be downregulated in HIV lipodystrophy, this miRNA has also been shown to be downregulated in circulating sEVs of patients with type 2 diabetes mellitus while demonstrating an inhibitory effect on diabetes-related inflammation ( 31 ). miR-324-5p overexpression has been linked to enhanced glucose uptake in oxygen glucose–deprived neurons ( 32 ) and has been reported to promote Wnt signaling ( 33 ). Consistent with this, we found downregulated Wnt signaling in adipocytes following treatment with anti–miR-324-5p.…”