Omentin-1 May Be One Treatment Factor for Intravenous Thrombolysis of Acute Cerebral Infarction Through the Inhibition of NLRP3 Ubiquitination by AMPK Function: Preliminary Findings.

BACKGROUND: Acute cerebral infarction (ACI) is a common neurological disease that is associated with high morbidity, disability and mortality rates. At present, antiplatelet therapy is a necessary treatment for ACI. The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. OBJECTIVE: The present study aimed to investigate the effects of omentin-1 on the intravenous thrombolysis of ACI. MATERIAL AND METHODS: The mouse model of ACI was induced using male C57BL/6 mice through middle cerebral artery occlusion (MCAO). Meanwhile, the murine BV2 microglial cells were pretreated with 0.1 mg/ml of lipopolysaccharide (LPS), and then induced with 2 mM of adenosine triphosphate (ATP). RESULTS: The omentin-1 mRNA expression in patients receiving intravenous thrombolysis for ACI was down-regulated compared with the normal group. Additionally, the serum level of omentin-1 was negatively correlated with National Institute of Health Stroke Scale (NIHSS) score or serum level of IL-1ß or MMP-2 in patients receiving intravenous thrombolysis for ACI. Meanwhile, the serum mRNA expression of omentin-1 was positively correlated with Barthel index or high-sensitivity C-reactive protein (hs-CRP) in patients undergoing intravenous thrombolysis for ACI. As observed from the in vitro model, Omentin-1 reduced inflammation, promoted cell growth, alleviated ROS-induced oxidative stress, and enhanced AMPK activity through activating NLRP3 ubiquitination. Omentin-1 presented ACI in the mouse model of ACI. Regulating AMPK activity contributed to controlling the effects of Omentin-1 on the in vitro model. CONCLUSIONS: Omentin-1 reduced neuroinflammation and ROS-induced oxidative stress in the mouse model of ACI, which was achieved by inhibiting NLRP3 ubiquitination through regulating AMPK activity. Therefore, omentin-1 may serve as a treatment factor for the intravenous thrombolysis of ACI in further clinical application.

Bortezomib induces cellular senescence in A549 lung cancer cells by stimulating telomere shortening.

Bortezomib (BTZ) is a first-generation proteasome inhibitor with anti-tumor properties for multiple myeloma and mantle cell lymphoma. Increasing evidence has shown that BTZ exhibits toxic effects on diverse tumor cells, including non-small cell lung cancer (NSCLC) cells. However, the mechanism has not been fully evaluated. Here, we examined the regulatory effect of BTZ on cellular senescence, a potent tumor suppressive mechanism, in NSCLC cell lines. SA-ß-gal staining assay showed that BTZ caused a significant increase in ß-Gal positive A549 cells. BTZ also induced cell cycle arrest on G0/G1 phase in A549 cells. Furthermore, telomerase activity was markedly reduced in A549 cells treated with BTZ. BTZ reduced the expression levels of hTERT, and the key proteins binding to telomeric DNA, including POT1 and TIN2. It also induced the expressions of the cell cycle-associated tumor suppressors p53 and p21 in A549 cells. Moreover, hTERT overexpression abolished the effects of BTZ on A549 cells. These results show that BTZ induced cellular senescence by stimulating telomere shortening. Our results provide experimental data for the potential clinical application of BTZ in NSCLC treatment.

Circ_0025039 acts an oncogenic role in the progression of non-small cell lung cancer through miR-636-dependent regulation of CORO1C.

Non-small cell lung cancer remains the leading cause of cancer-related death worldwide. Circular RNA plays vital roles in NSCLC progression. This study is designed to reveal the role of circ_0025039 in NSCLC cell malignancy. The RNA expression of circ_0025039, microRNA-636 (miR-636), and coronin 1C was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell proliferation, migration, invasion, tube formation ability, sphere formation capacity, and apoptosis were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, transwell assay, tube formation assay, sphere formation assay, and flow cytometry analysis, respectively. Mouse model assay was conducted to reveal the effect of circ_0025039 silencing on tumor formation in vivo. The interaction between miR-636 and circ_0025039 or CORO1C was identified through dual-luciferase reporter and RNA pull-down assays. The expression of circ_0025039 and CORO1C was significantly increased, while miR-636 was decreased in NSCLC tissues and cells compared with controls. Circ_0025039 depletion repressed NSCLC cell proliferation, migration, invasion, tube-forming capacity, and sphere formation ability, but induced cell apoptosis. The neoplasm formation was repressed after circ_0025039 silencing. Additionally, circ_0025039 acted as a sponge for miR-636, which was found to target CORO1C. Importantly, the contribution of circ_0025039 to NSCLC progression was mediated by miR-636/CORO1C axis. Circ_0025039 silencing repressed NSCLC malignant progression by reducing CORO1C expression through miR-636, showing the possibility of circ_0025039 as a therapeutic target for NSCLC.

Syntenin overexpression in human lung cancer tissue and serum is associated with poor prognosis.

BACKGROUND: Lung cancer is the major malignant tumour. The present study was conducted to determine the expression level of syntenin in lung cancer tissues and serum from lung cancer patients and to explore its clinical significance. METHODS: Syntenin expression levels were determined in paraffin-embedded lung cancer tissue specimens (n = 191) using immunohistochemistry. The mRNA expressions of syntenin in fresh lung cancer tissues and the paracancerous tissues were examined by RT-qPCR (n = 25). Syntenin and VEGF expression levels were measured in serum from patients with lung cancer (n = 60) and control subjects (n = 30) using ELISA. The associations between syntenin and the clinicopathological features or prognosis in 191 patients with lung cancer were analysed. The correlation between the syntenin and VEGF levels in serum from 60 lung cancer patients was analysed. RESULTS: The expression levels of syntenin were significantly higher in lung cancer tissues than in paracancerous tissues based on immunohistochemistry and RT-qPCR, and elevated syntenin expression was significantly associated with tumour size (P = 0.002), TNM stage (P = 0.020), tumour distant metastasis (P = 0.033), overall survival (OS) (P = 0.002) and progression-free survival (PFS) (P = 0.001). Multivariate analysis revealed that increased expression of syntenin was an independent risk factor for OS (P = 0.006) and PFS (P < 0.001) in lung cancer patients. The expression levels of syntenin and VEGF in serum from lung cancer patients were higher than those from control subjects (P < 0.001, P < 0.001, respectively), and their expression levels were positively correlated (r = 0.49, P < 0.001). CONCLUSIONS: Syntenin expression is upregulated in lung cancer patients, and its serum expression level is positively correlated with VEGF. Moreover, syntenin overexpression was correlated with poor prognosis in patients with lung cancer.