PurposeTo investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer.Materials and MethodsThe influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2α, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR.ResultsThe expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells.ConclusionLeptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression.
ABSTRACT. We examined whether erythropoietin (EPO) can inhibit adipogenic differentiation of mesenchymal stem cells (MSCs) in the mouse bone marrow and its underlying mechanism. We separated and extracted mouse bone marrow MSCs and induced adipogenic differentiation using 3-isobutyl-1-methylxanthine, insulin, and dexamethasone. Different concentrations of EPO were added to the cells and observed by Oil Red O staining on the 20th day to quantitatively analyze the degree of cell differentiation. mRNA expression levels of peroxysome proliferator-activated receptor g (PPARg), CCAAT enhancer binding protein a, and adiponectin were analyzed by real-time quantitative polymerase chain reaction, and the activity of PPARg, extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (p38 MAPK) were determined by western blotting. EPO significantly inhibited adipogenic differentiation of MSCs after 20 days and reduced absorbance values by Oil Red O staining without affecting proliferation (2015) activity. EPO downregulated the mRNA expression of PPARg, CCAAT enhancer binding protein a, fatty acid binding protein 4, and adiponectin during adipogenesis and increased protein phosphorylation of ERK, p38 MAPK, and PPARg during differentiation. EPO downregulated the mRNA expression of PPARg, CCAAT enhancer binding protein a, fatty acid binding protein 4, and adiponectin by increasing protein phosphorylation of ERK, p38 MAPK, and PPARg during differentiation, which inhibited adipogenic differentiation of MSCs.
Glioblastoma (GBM) is the most common and fatal malignant tumor type of the central nervous system. GBM affects public health and it is important to identify biomarkers to improve diagnosis, reduce drug resistance and improve prognosis (e.g., personalized targeted therapies). Hedgehog (HH) signaling has an important role in embryonic development, tissue regeneration and stem cell renewal. A large amount of evidence indicates that both normative and non-normative HH signals have an important role in GBM. The present study reviewed the role of the HH signaling pathway in the occurrence and progression of GBM. Furthermore, the effectiveness of drugs that target different components of the HH pathway was also examined. The HH pathway has an important role in reversing drug resistance after GBM conventional treatment. The present review highlighted the relevance of HH signaling in GBM and outlined that this pathway has a key role in the occurrence, development and treatment of GBM. Contents 1. Introduction 2. Overview of GBM 3. The HH signaling pathway 4. Molecular mechanisms of the HH signaling pathway in GBM 5. Targeting the HH signaling pathway in GBM 6. HH pathway and immunotherapy 7. Discussion 8. Conclusion
The rapid increase in cancer morbidity and mortality worldwide is a major challenge for public health providers. Therefore, there is an urgent need to explore the molecular mechanism of tumorigenesis and identify potential diagnostic biomarkers and therapeutic methods. Circular RNA (circRNA) is characterized by a stable structure and tissue-specific expression; these features are useful in medical research and clinical applications. In recent years, with the development of high-throughput sequencing technology, the potential use of circRNA in cancer prognosis and treatment has been extensively explored. Abnormal circRNA expression interferes with specific signaling pathways such as the MAPK pathway; this phenomenon may provide potential diagnostic biomarkers and new therapeutic targets. The present article discusses the research progress on the regulatory roles of MAPK/ERK pathway-related circRNA molecules in the development and progression of different types of tumors. This review may provide insight into the development of circRNA-based cancer management strategies.
Circular RNA (circRNA), a recently identified type of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5' cap structure nor a 3' polyadenylated tail. Due to their lack of free ends, circRNAs are not easily cleaved by RNase R, thus avoiding degradation and being more stable than linear RNAs. Recent studies have suggested that circRNAs play a crucial role in regulating gene expression by acting as microRNAs sponges, RNA binding protein sponges and translational regulators. Currently, circRNAs are hot research topics due to their close association with the development of cancer and other diseases. Hypoxia is the most common microenvironment during tumor growth, and hypoxia-inducible factors have different effects on tumor growth and influence important cancer characteristics, including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune response, invasion and metastasis. The present review aimed to study the biogenesis and mechanisms of gene regulation of circRNAs in hypoxia, to summarize the latest studies on circRNAs as potential diagnostic and prognostic biomarkers in hypoxia, and to understand the role of circRNAs in the process of tumor drug resistance under hypoxia.
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