LncRNA GAS5 regulates ischemic stroke as a competing endogenous RNA for miR-137 to regulate the Notch1 signaling pathway

Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro-vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen-glucose deprivation (OGD)-cultured mice brain micro-vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR-18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase-3 activity and cell apoptosis in OGD-cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR-18a, thereby regulating the de-repression of its endogenous target HIF-1α and promoting BMEC survival through HIF-1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF-1α/VEGF signaling through acting as a ceRNA for miR-18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease.

LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF-1α/VEGF signaling in ischemic stroke.

CNS injuries, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and cerebral ischemic stroke, are important causes of death and long-term disability worldwide. As an important class of pervasive genes involved in many pathophysiological processes, long non-coding RNAs (lncRNAs) have received attention in the past decades. Multiple studies indicate that lncRNAs are abundant in the CNS and have a key role in brain function as well as many neurological disorders, especially in CNS injuries. Several investigations have deciphered that regulation of lncRNAs exert pro-angiogenesis, anti-apoptosis, and anti-inflammation effects in CNS injury via different molecules and pathways, including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), Notch, and p53. Thus, lncRNAs show great promise as molecular targets in CNS injuries. In this article, we provide an updated review of the current state of our knowledge about the relationship between lncRNAs and CNS injuries, highlighting the specific roles of lncRNAs in CNS injuries.

Long Non-coding RNA in CNS Injuries: A New Target for Therapeutic Intervention.

Objective: The present study was designed to investigate the molecular mechanism and biological roles of lncRNA brain-derived neurotrophic factor antisense (lncRNA BDNF-AS) in acute spinal cord inj...

https://www.tandfonline.com/doi/pdf/10.1080/15476286.2018.1493333

Knockdown of lncRNA BDNF-AS suppresses neuronal cell apoptosis via downregulating miR-130b-5p target gene PRDM5 in acute spinal cord injury.

Long noncoding RNA BDNF-AS is a potential biomarker and regulates cancer development in human retinoblastoma.

Long noncoding RNA BDNF-AS regulates ketamine-induced neurotoxicity in neural stem cell derived neurons.

Diseases affecting cardiovascular system are ranked as a top most cause of morbidity and mortality. Herein, a novel class sulphonamides-1,3,5-triazine conjugates have been synthesized and tested for inhibitory activity against MMP-2 and MMP-9. The results of the study showed that these molecules efficiently inhibit MMP-9 than MMP-2, revealing compound 8e as the most potent inhibitor (IC50  = 2.34 ± 0.56 nm). Due to involvement of MMP-9 in many cardiovascular diseases, particularly in myocardial ischaemia (MI), compound 8e was further subjected for the determination of the protective effect on isoproterenol (ISO)-induced myocardial injury in rats.

Jia-Li Zhou

Papers

Long noncoding RNA BDNF-AS regulates ketamine-induced neurotoxicity in neural stem cell derived neurons.

Cardioprotective effect of novel sulphonamides‐1,3,5‐triazine conjugates against ischaemic–reperfusion injury via selective inhibition of MMP‐9