LncRNA KCNQ1OT1 contributes to oxygen-glucose-deprivation/reoxygenation-induced injury via sponging miR-9 in cultured neurons to regulate MMP8.

Our study proposed to investigate the function of potassium voltage-gated channel sub-family Q member 1 opposite strand 1 (KCNQ1OT1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanism. We constructed an oxygen-glucose-deprivation/reoxygenation (OGD/R) model using the primary cortical neurons to mimic the cerebral I/R injury in vitro. Small inference RNA (siRNA) was used to silencing KCNQ1OT1. Dual luciferase assay was conducted to verify the interaction between KCNQ1OT1 and miR-9 and interaction between miR-9 and MMP8. CCK8 assay and flow cytometry analysis were applied for determing the viability and apoptosis of neurons, accordingly. QPCR and Western blot were performed to determine the RNA and protein expression. Our outcomes revealed that the expression of KCNQ1OT1 in cultured neurons was notably enhanced after suffered to OGD/R. Knockdown of KCNQ1OT1 weakened OGD/R-induced injury in neurons. Moreover, depletion of KCNQ1OT1 lead to the up-regulation of miR-9 and down-regulation of MMP8. Dual luciferase target validation assays demonstrated that KCNQ1OT1 directly interact with miR-9 and MMP8 is a direct target of miR-9, suggesting that KCNQ1OT1/miR-9/MMP8 might constitute the competing endogenous RNA (ceRNA) mechanism. Knockdown of MMP8 or up-regulation of miR-9 also could weaken OGD/R-induced injury. Furthermore, cells co-transfected with si-KCNQ1OT1, miR-9 mimic and si-MMP8 could significantly abolish the injury on neurons caused by OGD/R. Taken together, our data manifested that KCNQ1OT1 possibly acts as a facilitator in cerebral I/R injury through modulating miR-9/MMP8 axis as a ceRNA.

Altered DMN functional connectivity and regional homogeneity in partial epilepsy patients: a seventy cases study.

PURPOSE: Clinically diagnosed partial epilepsy is hard to be functionally diagnosed by regular electroencephalograph (EEG) and conventional magnetic resonance imaging (MRI). By collecting transient brain regional signals, blood oxygenation level-dependent (BOLD) function MRI (BOLD-fMRI) can provide brain function change information with high accuracy. By using resting state BOLD-fMRI technique, we aim to investigate the changes of brain function in partial epilepsy patients. METHODS: BOLD-fMRI scanning was performed in 70 partial epilepsy and 70 healthy people. BOLD-fMRI data was analyzed by using the Regional Homogeneity (ReHo) method and functional connectivity of Default Mode Network (DMN) methods. The abnormal brain functional connectivity in partial epilepsy patients was detected by Statistical Parametric Mapping 8 (SPM8) analysis. RESULTS: Compared to healthy group, epilepsy patients showed significant decreased ReHo in left inferior parietal lobule/pre- and post-central gyrus, right thalamus/paracentral lobule/Cerebellum anterior and posterior Lobe, bilateral insula. The DMN functional connectivity regions decreased significantly in right uncus, left Inferior parietal lobule, left supramarginal gyrus, left uncus, left parahippocampa gyrus, and left superior temporal gyrus, in epilepsy patients, compared to healthy controls. SIGNIFICANCE: This study clarified that both ReHo and functional connectivity of DMN decreased in partial epilepsy patients compared to healthy controls. While left inferior parietal lobule was detected in both ReHo and DMN, many other identified regions were different by using these two BOLD-fMRI techniques. We propose that both ReHo and DMN patterns in BOLD-fMRI may suggest networks responsible for partial epilepsy genesis or progression.