Mir-338-3p targeting THBS1 attenuates glioma progression by inhibiting the PI3K/Akt pathway.

BACKGROUND: Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction and western blotting were performed to evaluate the levels of miR-338-3p, THBS1, and PI3K/Akt phosphorylation-related proteins. TargetScan software predicted that miR-338-3p targeted THBS1. This was confirmed by performing the dual-luciferase assay. Wound-healing and cell-counting-kit-8 experiments were performed to analyze how THBS1 and miR-338-3p affect the ability of glioma cells to migrate and proliferate. The effect of miR-338-3p on tumorigenicity in mice was also analyzed. RESULTS: miR-338-3p downregulation was observed in gliomas, whereas THBS1 showed the opposite trend. By suppressing the PI3K/Akt signaling pathway activation, miR-338-3p overregulated the ability of glioma cells to migrate and proliferate in vitro. Additionally, miR-338-3p inhibited the development of glioma tumors in vivo. Moreover, miR-338-3p directly targeted THBS1. THBS1 overexpression promoted glioma cell migration and proliferation by increasing PI3K/Akt phosphorylation. Nonetheless, miR-338-3p overregulation alleviated the effects of THBS1 overexpression. CONCLUSION: The miR-338-3p/PI3K/Akt/THBS1 regulatory axis can modulate the progression of glioma cell proliferation and migration; thus, it can be considered a therapeutic biomarker.

Screening of liothyronine network pharmacology role in the treatment of ischemic stroke and molecular mechanism.

OBJECTIVE: The present study aimed to elucidate mechanisms of liothyronine on the treatment of ischemic stroke (IS). METHODS: Differential analysis based on R limma package was used to identify differentially expressed genes, which were then mapped into the connectivity map database for identification of liothyronine associated with IS. Tumor necrosis factor (TNF) signaling pathway was verified through pathway enrichment analysis via Enrichr online. Ischemia stroke mouse model was built up for further analysis. Infarct area and regional cerebral blood flow (rCBF) were measured by 2, 3, 5-triphenyltetrazolium chloride and laser Doppler flowmetry, respectively. Light microscope was used for the evaluation of body weight and dark neurons. Serum TXB2 , 6-Keto-PGF1a , TNF-α, and interleukin-6 (IL-6) levels in mice were measured using enzyme-linked immuno sorbent assay. In addition, relative protein expression levels of brain-derived neurotrophic factor, nestin, and Sox2 were detected by Western blot analysis. RESULTS: Liothyronine with a negative connectivity was identified as one promising treatment for IS through TNF signaling pathway. The experimental results showed that liothyronine treatment significantly meliorated infarct area and the number of dark neurons in IS mice. Liothyronine greatly ameliorated the expression levels of TXB2 and 6-Keto-PGF1a . Besides, rCBF and body weight change of IS mice were increased gradually with increase of drug concentration. Based on pathway enrichment analysis, anti-inflammatory response (TNF-α and IL-6) relevant to TNF signaling pathway was identified, which was further validated in vitro. Furthermore, proteins as neural stem cell markers made a difference with liothyronine treatment. CONCLUSION: Liothyronine may be a novel therapeutic component to exploit an effective medicine for the treatment of IS.

Prefoldin 6 promotes glioma progression via the AKT signalling pathway.

Gliomas are one of the most aggressive primary tumours, accounting for 81% of malignant brain tumours, and are associated with a significant mortality. Therefore, the elucidation of the molecular mechanism underlying glioma progression and identification of promising treatment targets are necessary. Here, the expression of prefoldin (PFDN) 6 in human glioma tissues and cell lines was evaluated using immunohistochemistry and quantitative polymerase chain reaction. Celigo and CCK-8 assays were performed for assessing cell viability. Flow cytometry was used to analyse apoptosis and cell cycle distribution. Wound-healing and transwell assays were performed to observe cell migration. Lastly, xenograft models were developed for the in vivo validation of the results, and a human phospho-kinase array was used to explore the downstream signalling pathways. PFDN6 was upregulated in gliomas, and PFDN6 overexpression was significantly correlated with a low survival rate, estimated glomerular filtration rate (EGFR) expression, and tumour grade and recurrence. Moreover, PFDN6 knockdown significantly attenuated cell proliferation and migration, induced apoptosis, and blocked cell cycle progression in the G2 phase, which was further confirmed in the in vivo experiments. Mechanistically, the effects of PFDN6 may be mediated via the AKT signalling pathway. In conclusion, we showed that PFDN6 promotes glioma development by activating AKT signalling and emphasised the potential of PFDN6 as a crucial target in glioma therapy.

Characteristics and prognostic factors of age-stratified high-grade intracranial glioma patients: A population-based analysis.

We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20-39 years old (1,043 patients), 40-59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20-39 yr: HR = 6.41; 40-59 yr: HR = 4.84; >60 yr: HR = 5.06; cause-specific survival: 20-39 yr: HR = 5.87; 40-59 yr: HR = 4.01; >60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.