Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource.

Cytosolic double‐stranded DNA (dsDNA) is a danger signal that is tightly monitored and sensed by nucleic acid‐sensing pattern recognition receptors. We study the inflammatory cascade on dsDNA recognition and investigate the neuroprotective effect of cyclic GMP‐AMP (cGAMP) synthase (cGAS) antagonist A151 and its mechanisms of neuroprotection in a mouse model of experimental stroke. Here, we found that cerebral ischemia promoted the release of dsDNA into the cytosol, where it initiated inflammatory responses by activating the cGAS. A151 effectively reduced the expression of cGAS, absent in melanoma 2 (AIM2) inflammasome, and pyroptosis‐related molecules, including caspase‐1, gasdermin D, IL‐1β, and IL‐18. Furthermore, mice treated with A151 showed a dampened immune response to stroke, with reduced counts of neutrophils, microglia, and microglial production of IL‐6 and TNF‐α after MCAO. Moreover, A151 administration significantly reduced infarct volume, attenuated neurodeficits, and diminished cell death. Notably, the protective effect of A151 was blocked in a microglia‐specific cGAS knockout mouse. These findings offer unique perspectives on stroke pathogenesis and indicate that inhibition of cGAS could attenuate brain inflammatory burden, representing a potential therapeutic opportunity for stroke.

Cross-talk between competitive endogenous RNAs (ceRNAs) through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of cancers. However, a global view of their system-level properties across various types of cancers is still unknown. Here, we constructed the mRNA related ceRNA–ceRNA interaction landscape across 20 cancer types by systematically analyzing molecular profiles of 5203 tumors and miRNA regulations. Our study highlights the conserved features shared by pan-cancer and higher similarity within similar origin cell type. Moreover, a core ceRNA network was identified. Function analysis identified a common theme of cancer hallmarks, however they exhibit phenotype-specific connectivity patterns. Besides, we found a marked rewiring in the ceRNA program between various cancers, and further revealed conserved and rewired network ceRNA hubs in each cancer, which were tensely competitive interactions to constitute conserved and cancer-specific modules. By providing mechanistic linkage between known cancer miRNAs, their mediated ceRNA–ceRNA interactions, and the associations with known cancer hallmarks, the inferred cancer ceRNA–ceRNA interaction landscape will serve as a powerful public resource for further biological discoveries of tumorigenesis.

Circulating neutrophil extracellular traps (NETs) resistant to t‐PA have not been studied completely although NETs in thrombi may contribute to tissue plasminogen activator (t‐PA) resistance. This research intended to elucidate whether circulating NETs are associated with t‐PA resistance and the underlying mechanism. The levels of NETs were detected in the circulating neutrophils, ischemic brain tissue of acute ischemic stroke (AIS) patients, and transient middle cerebral artery occlusion (tMCAO) models. NET formation in blood, thrombi, and ischemic brain tissue of mice were analyzed by immunofluorescence. Exposed phosphatidylserine (PS) was assessed using flow cytometry and confocal microscopy. Procoagulant activity (PCA) was evaluated using fibrin formation assays, thrombin, and purified coagulation complex. The plasma levels of NETs in AIS patients were significantly higher than those in healthy individuals. After thrombolysis, a significant increase was noted in NET markers in no‐improvement patients, while the changes in improvement patients were not significant. Importantly, NETs were decorated with von Willebrand factor (vWF) and plasminogen activator inhibitor‐1 (PAI‐1) in the blood and thrombi, which could reverse the fibrinolytic effects. In addition, NETs activated platelets (PLTs) and endothelial cells (ECs), stimulating a procoagulant phenotype and facilitating vWF and PAI‐1 release. DNase I, activated protein C (APC), and sivelestat markedly inhibited these effects. Furthermore, targeting NETs protected mice from tMCAO‐induced cerebral ischemia, possibly by regulating vWF and PAI‐1. In summary, NETs may contribute to t‐PA resistance in AIS through activation of PLTs and ECs. Strategies against NETs may present a promising therapeutic approach to improve the thrombolysis efficiency of t‐PA in AIS patients.

Inflammation eliminates pathogenic infections while also threatening the integrity of the central nervous system. In this study, using in vivo and in vitro models of acute neuroinflammation, we investigated the mechanisms by which inflammation and astrocytes affect neuronal apoptosis. The in vitro model mimicked acute neuroinflammation by incubation in IFN-γ-containing media with primary cultured cerebellar granule neurons, with or without cultured astrocytes. This quickly induced neuronal apoptosis characterized by cleaved caspase-3 expression, Hoechst 33342 staining, and intercellular Ca2+ influx, whereas the presence of astrocytes significantly protected neurons from these effects. IFN-γ in the inflammation media also promoted astrocyte secretion of IL-6, essential for protection. The supernatants of rat peripheral blood mononuclear cells stimulated by lymphocyte mitogen lipopolysaccharide or concanavalin A were used as inflammation media to verify the results. The in vivo model involved a peripheral challenge with lipopolysaccharide, with or without recombinant IFN-γ, in C57BL/6 mice. This confirmed the in vitro results: anti-IFN-γ antibodies exacerbated the acute course of neuroinflammation and led to neurocyte apoptosis in vivo. The pro-inflammatory cytokine IFN-γ provided neuroprotection during acute neuroinflammation via induction of astrocyte-secreted IL-6. The findings provide novel insights into the mechanisms of neuroprotection by IFN-γ during acute neuroinflammation, and may impact therapies for inflammation-related central nervous system injury and disease.