Circular RNAs (circRNAs) are a novel category of non-coding RNAs, and they have been identified to participate in glioma tumorigenesis. Here we investigated the functions of circRNA circSCAF11 in glioma genesis, and we unveiled its molecular mechanism in the pathophysiological process. Expression levels of circSCAF11, miR-421, and SP1 mRNA were measured using RT-PCR. Proteins were measured using western blotting. The tumor phenotypes of glioma cells were detected using flow cytometry and Cell Counting Kit-8 (CCK-8), transwell, and xenograft mouse assays. The combination within circSCAF11, miR-421, and SP1 was validated using luciferase reporter assay or RNA pull-down assay. The binding of transcription factor SP1 with vascular endothelial cell growth factor A (VEGFA) promoter was inspected using chromatin immunoprecipitation (ChIP). circSCAF11 expression was found to be significantly upregulated in the glioma tissue specimens and cell lines. The ectopic overexpression of circSCAF11 was closely correlated with the poor clinical outcome of glioma patients. Functionally, knockdown of circSCAF11 inhibited the proliferation, invasion, and tumor growth and induced the G0/G1 phase arrest. Mechanically, circSCAF11 positively regulated the SP1 expression through sponging miR-421. Moreover, transcription factor SP1 activated the transcription of VEGFA, constructing the circSCAF11/miR-421/SP1/VEGFA axis in the glioma genesis. The findings in this research illustrate that circSCAF11 accelerates glioma tumorigenesis through the miR-421/SP1/VEGFA axis, providing a potential target for circRNA and glioma treatment.

Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3'-UTR. Functional experiments revealed that UCA1 acted as an miR-122 "sponge" to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma.

Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptive responses that provide a defense against additional stress. Epileptic preconditioning protects neurons against status epilepticus and ischemia; however, it is not known if the converse is true. During hypoxia/ischemia (H/I), lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporter 4 (MCT4) in astroglia. The present study investigated whether H/I preconditioning can provide protection to neurons against epilepsy through upregulation of MCT4 expression in astrocytes in vitro and in vivo. An oxygen/glucose deprivation protocol was used in primary astrocyte cultures, while rats were subjected to an intermittent hypoxia preconditioning (IHP) paradigm followed by lithium-pilocarpine-induced epilepsy as well as lactate transportation inhibitor injection, with a subsequent evaluation of protein expression as well as behavior. H/I induced an upregulation of MCT4 expression, while an IHP time course of 5 days provided the greatest protection against epileptic seizures, which was most apparent by 3 days after IHP. However, lactate transport function disturbances can block the protective effect induced by IHP. These findings provide a potential basis for the clinical treatment of epilepsy.

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Traumatic brain injury (TBI) is a universal leading cause of long-term neurological disability and causes a huge burden to an ever-growing population. Moderate intensity of treadmill exercise has been recognized as an efficient intervention to combat TBI-induced motor and cognitive disorders, yet the underlying mechanism is still unclear. Ferroptosis is known to be highly implicated in TBI pathophysiology, and the anti-ferroptosis effects of treadmill exercise have been reported in other neurological diseases except for TBI. In addition to cytokine induction, recent evidence has demonstrated the involvement of the stimulator of interferon genes (STING) pathway in ferroptosis. Therefore, we examined the possibility that treadmill exercise might inhibit TBI-induced ferroptosis via STING pathway. In this study, we first found that a series of ferroptosis-related characteristics, including abnormal iron homeostasis, decreased glutathione peroxidase 4 (Gpx4), and increased lipid peroxidation, were detected at 44 days post TBI, substantiating the involvement of ferroptosis at the chronic stage following TBI. Furthermore, treadmill exercise potently decreased the aforementioned ferroptosis-related changes, suggesting the anti-ferroptosis role of treadmill exercise following TBI. In addition to alleviating neurodegeneration, treadmill exercise effectively reduced anxiety, enhanced spatial memory recovery, and improved social novelty post TBI. Interestingly, STING knockdown also obtained the similar anti-ferroptosis effects after TBI. More importantly, overexpression of STING largely reversed the ferroptosis inactivation caused by treadmill exercise following TBI. To conclude, moderate-intensity treadmill exercise rescues TBI-induced ferroptosis and cognitive deficits at least in part via STING pathway, broadening our understanding of neuroprotective effects induced by treadmill exercise against TBI.