MiR-497 Suppresses YAP1 and Inhibits Tumor Growth in Non-Small Cell Lung Cancer

Background/Aims: To investigate the expression, clinical significance and the cellular effects of miR-497 in non-small cell lung cancer (NSCLC). Methods: NSCLC cells were transiently transfected with miR-497 mimics or siRNA to up-regulate or down-regulate expression. Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA level of miR-497. Luciferase assays, colony formation assays and BrdU incorporation assays were performed to identify the targets and role of miR-497 in NSCLC cells. Finally, the abundance of miR-497 was analyzed in a total of 51 NSCLC specimens. Results: The transcript levels of miR-497 were significantly decreased in NSCLC tissue (25/30; 83.3%). Low miR-497 levels in tumor tissue correlated with advanced pT stage. Additionally, miR-497 transcript levels correlated with overall survival of NSCLC patients (n = 51, p = 0.022). Overexpression of miR-497 inhibited the proliferation of NSCLC cell and down-regulation of miR-497 resulted in elevated NSCLC growth. Exogenous over-expression of YAP1 partially eliminated miR-497-induced cell growth. Conclusion: miR-497 plays an important role in inhibiting the proliferation of NSCLC by targeting YAP1. Our results suggest that miR-497 is a potential therapeutic target in treating patients with NSCLC

Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma

Hypoxia inducible factor 1 (HIF-1) is a transcription factor composed of two subunits, namely, HIF-1α and HIF-1β, in which HIF-1β is constitutively expressed. HIF-1 upregulates several hypoxia-responsive proteins, including angiogenesis factors, glycolysis solution enzymes, and cell survival proteins. HIF-1 is also associated with the degree of inflammation in the tumor region, but the exact mechanism remains unclear. This study aims to identify the molecular mechanism of recruiting monocytes/macrophages by HIF-1α in pancreatic ductal adenocarcinoma (PDAC) and the effects of macrophages on pancreatic stellate cells (PSCs). Immunohistochemistry (IHC) was performed for cluster of differentiation 68 (CD68), HIF-1α, and chemical chemokines 2 (CCL2). Western blot, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation assay, and The Cancer Genome Atlas (TCGA) were used to verify the correlation between HIF-1α and CCL2 at protein and nucleic acid levels. Monocytes/macrophages were co-cultured with PSCs to observe their interaction. Samples showed significant correlation between CD68 and HIF-1α (t-test, p < 0.05). HIF-1α recruited monocytes/macrophages by promoting CCL2 secretion. Moreover, macrophages could accelerate the activation of PSCs. HIF-1α might promote inflammation and fibrosis of PDAC through CCL2 secretion, which may provide a novel target to treat PDAC patients

The maintenance of modified electroconvulsive therapy combined with risperidone is better than risperidone alone in preventing relapse of schizophrenia and improving cognitive function

ABSTRACT Objective To evaluate the effect of maintenance modified electroconvulsive therapy (MECT) on schizophrenic patients. Methods From June 2012 to June 2014, 62 patients with schizophrenia, who had recovered from a successful course of acute MECT, were recruited. Thirty-one patients received maintenance MECT and risperidone, as the experimental group. Another 31 patients were enrolled in the control group, and received risperidone only. The effects on cognitive functions, clinical symptoms and relapse rate were determined. Results Patients in the experimental group had a lower relapse rate and longer relapse-free survival time than the controls. Relative to the baseline evaluation, patients showed statistically significant improvement in verbal memory and visual memory. At the final assessment, the scores of verbal and visual memory were remarkably lower in the experimental group than the controls but there was no significant difference in other tests. Conclusion Maintenance MECT plus medication is superior to medication alone in preventing relapse and improving cognitive function

Fascin Controls Metastatic Colonization and Mitochondrial Oxidative Phosphorylation by Remodeling Mitochondrial Actin Filaments

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The disruption of mtF-actin abrogates fascin-mediated lung cancer metastasis. Conversely, restoration of mitochondrial respiration by using yeast NDI1 in fascin-depleted cancer cells is able to rescue lung metastasis. Our findings indicate that the dysregulated actin cytoskeleton in metastatic lung cancer could be targeted to rewire mitochondrial metabolism and to prevent metastatic recurrence