Circ_0101874 overexpression strengthens PDE4D expression by targeting miR-335-5p to promote neuronal injury in ischemic stroke.

BACKGROUND: Ischemic stroke has been a public concern, while its pathogenesis is not fully understood. Increasing evidence suggests that circular RNAs (circRNAs) are involved in this disorder. The purpose of this study was to explore the role of circ_0101874 in ischemic stroke. METHODS: The in vivo model of ischemic stroke was established in mice with middle cerebral artery occlusion (MCAO) treatment. The in vitro model of ischemic stroke was established in SK-N-SH cells with oxygen-glucose deprivation (OGD) treatment. The expression of circ_0101874, miR-335-5p and phosphodiesterase 4D (PDE4D) mRNA was measured by quantitative real-time PCR (qPCR). The release of inflammatory factors was checked by ELISA. Cell viability, cell proliferation and cell apoptosis were detected using CCK-8 assay, EdU assay and flow cytometry assay, respectively. The protein levels of cyclinD1, cleaved-caspase-3 and PDE4D were detected by western blot. The interaction between miR-335-5p and circ_0101874 or PDE4D was validated by dual-luciferase reporter assay and RIP assay. RESULTS: Circ_0101874 was highly expressed in MCAO animal models and OGD-induced SK-N-SH cells. Circ_0101874 knockdown suppressed OGD-enhanced inflammation, cell apoptosis and oxidative stress and promoted OGD-inhibited cell viability and cell proliferation in SK-N-SH cells. Circ_0101874 directly bound to miR-335-5p, and miR-335-5p inhibition reversed the effects of circ_0101874 knockdown. PDE4D was a target gene of miR-335-5p, and PDE4D overexpression recovered OGD-promoted SK-N-SH cell injuries that were blocked by miR-335-5p enrichment. Circ_0101874 bound to miR-335-5p to enhance the expression of PDE4D. CONCLUSION: Circ_0101874 knockdown alleviated OGD-induced neuronal cell injury by suppressing PDE4D via regulating miR-335-5p.

LINC00839 Regulates Proliferation, Migration, Invasion, Apoptosis and Glycolysis in Neuroblastoma Cells Through miR-338-3p/GLUT1 Axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are related to the development and treatment of neuroblastoma. The lncRNA LINC00839 is dysregulated in neuroblastoma, while its function and mechanism in neuroblastoma development remain largely unclear. METHODS: The tumor and adjacent noncancerous tissues were collected from 48 neuroblastoma patients. LINC00839, glucose transporter 1 (GLUT1) and microRNA-338-3p (miR-338-3p) abundances were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration, invasion and glycolysis were assessed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing, transwell, glucose uptake and lactate production. The target relationship of miR-338-3p and LINC00839 or GLUT1 was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. The function of LINC00839 on neuroblastoma cell growth in vivo was tested via a xenograft model. RESULTS: LINC00839 and GLUT1 abundances were increased in neuroblastoma tissues and cell lines. The high expression of LINC00839 and GLUT1 indicated the lower overall survival. LINC00839 interference constrained neuroblastoma cell proliferation, migration, invasion and glycolysis, and facilitated apoptosis. GLUT1 overexpression or miR-338-3p knockdown could mitigate the influence of LINC00839 silence on neuroblastoma cell processes. LINC00839 could regulate GLUT1 expression via miR-338-3p. LINC00839 knockdown reduced neuroblastoma cell growth in xenograft model. CONCLUSION: LINC00839 silence repressed neuroblastoma cell proliferation, migration, invasion and glycolysis and promoted apoptosis via regulating miR-338-3p/GLUT1 axis.