Ischemic stroke is a devastating condition with a high burden of neurological disability and death. The aim of this study was to explore the potential long noncoding RNA (lncRNA) biomarkers underlying the mechanism of stroke. The Subpathway-LNCE method, which was specifically designed to identify lncRNAs competitively regulated functions in diseases, was applied in ischemic stroke dataset to identify ischemic-stroke-associated dysfunctional subpathway that regulated by lncRNAs. At first, based on the shared microRNA (miRNA) between miRNA-messenger RNA (mRNA) and lncRNA-miRNA interactions, lncRNA-mRNA interactions were constructed. Then, the transcription profiling of 18 631 genes was downloaded from Array Express database and was preprocessed, including normalization and gene expression difference (DEG) analysis, to identify candidate differential pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Next, the pathway-lncRNA-mRNA networks were constructed by linking lncRNAs to candidate differential pathways. At last, there were 11 lncRNAs were identified in the top three subpathways as hub-lncRNAs totally, including LINC00240, LINC00472,

Purpose: The long intergenic non-protein coding RNA 1094 (LINC01094) plays a vital role in the oncogenicity of clear cell renal cell carcinoma. However, its expression profile and detailed roles in glioblastoma (GBM) remain unknown. In this study, we mainly investigated the expression and roles of LINC01094 in GBM and focused on the mechanism by which LINC01094 regulates the malignant characteristics of GBM. Patients and Methods: LINC01094 expression in GBM was determined with quantitative reverse transcription polymerase chain reaction. The proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo of GBM cells were evaluated using Cell Counting Kit-8 assay, flow cytometry analysis, migration assay, invasion assay, and tumor xenograft models, respectively. Results: LINC01094 was overexpressed in GBM tissues and cell lines. Moreover, increased LINC01094 expression was associated with adverse clinicopathological parameters in patients with GBM. Loss of LINC01094 inhibited GBM cell proliferation, migration, and invasion; promoted cell apoptosis; and suppressed tumor growth in vivo. Mechanically, LINC01094 functioned as a molecular sponge for microRNA-577 (miR-577) and consequently enhanced the expression of brain-derived neurotrophic factor (BDNF) in GBM cells. Both miR-577 inhibition and BDNF expression enhancement reversed LINC01094 deficiency-mediated inhibition of malignant processes in GBM cells. Conclusion: Our results verified the involvement of the LINC01094/miR-577/BDNF pathway in GBM cells and its enhancing effects on the aggressive behaviors of GBM cells in vitro and in vivo. This pathway may be a novel and promising focus for the future development of targeted therapies for GBM.

Background:The participation of activating transcription factor 3 (ATF3) in transient middle cerebral artery occlusion and reperfusion injury has been reported. However, the precise mechanism of ATF3 in cerebral ischemia is little known so far. Thus, the study examines the mechanism of action underlying the protective role of ATF3 following middle cerebral artery occlusion (MCAO) in rats. Methods and results:The MCAO rats exhibited reduced body weight and motor ability, while increased neurological deficits and brain infarct volume. Gene ontology (GO) enrichment and KEGG pathway analyses revealed that differentially expressed genes were mainly enriched in the TLR4/NF-κB signaling. Moreover, ATF3 was the most differentially expressed gene in brain tissues of MCAO rats versus sham-operated rats, which could bind to CCL2. ATF3 was reduced in MCAO rats, and ATF3 inhibited CCL2 expression to mediate the TLR4/NF-κB signaling. Functionally, ATF3 inhibited neuronal apoptosis, microglia activation, and pro-inflammatory cytokine production to alleviate brain injury in rats. By contrast, CCL2 was overexpressed in neurons and microglia, and CCL2 mitigated the effects of ATF3 to exacerbate brain injury in rats. Conclusion:Our findings suggested that ATF3 repressed neuronal apoptosis and microglia activation caused by cerebral ischemia via targeting CCL2 and mediating the TLR4/NF-κB signaling.