Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

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Background: Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms.Methods: Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain-and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/β-catenin pathway was measured. In vivo experiments were performed as well.Results: High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/β-catenin pathway. Artificial silencing of NCK1-AS1 or upregulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/β-catenin pathway. The in vitro results were reproduced in in vivo experiments.Conclusions: Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/βcatenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.

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Background Circular RNAs serve as key players in the development of tumorigenesis and chemoresistance. Circular RNA CEP128 has been reported to be involved in the development of chemoresistance. However, the role of circular RNA CEP128 in the resistance of glioma cells to temozolomide has not yet been characterized. Methods The expression of circular RNA CEP128, miR-145-5p, and ATP-binding cassette super-family G member 2 was evaluated using quantitative real-time PCR and western blot. The effects of circular RNA CEP128 on glioma cell proliferation and chemoresistance were evaluated by cell count kit-8 assay and colony formation assay. Luciferase reporter assay was performed for target validation. Results Circular RNA CEP128 was upregulated in glioma tissues and cell lines. Moreover, circular RNA CEP128 expression was higher in temozolomide-resistant glioma cells compared with that in their parental cells. Knockdown of circular RNA CEP128 inhibited cell proliferation, reduced the expression of ATP-binding cassette super-family G member 2, as well as reduced resistance to temozolomide in glioma cells. Additionally, miR-145-5p was underexpressed in glioma cells as well as temozolomide-resistant glioma cells. Also, miR-145-5p was identified as a target of circular RNA CEP128. Overexpression of miR-145-5p inhibited the proliferation of U251/temozolomide cells and reduced the expression of ATP-binding cassette super-family G member 2, however, these changes induced by miR-145-5p overexpression were blocked by circular RNA CEP128 overexpression. Conclusion Knockdown of circular RNA CEP128 suppresses cell proliferation and improves the cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p, suggesting that circular RNA CEP128 might be a promising target for overcoming the resistance of glioma cells to temozolomide.