scholarly journals HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT / mTOR and MDM2 /p53 signaling pathway

2020 ◽  
Vol 11 (11) ◽  
pp. 3155-3167
Author(s):  
Zhigang Liang ◽  
Yuan Zhong ◽  
Lifei Meng ◽  
Yi Chen ◽  
Yahui Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
P53 Signaling ◽  
P53 Signaling Pathway

scholarly journals 125I Seed Promotes Apoptosis in Non-small Lung Cancer Cells via the p38 MAPK-MDM2-p53 Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Zhang ◽  
ZhiQiang Mo ◽  
Guangfeng Duan ◽  
Rijie Tang ◽  
Fujun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Purpose:125I seeds were effective in the treatment of non-small cell lung cancer in previous research. However, the exact signaling pathway-mediated apoptosis mechanism is still unclear. The present study analyzed the effects and potential mechanisms of 125I seed on the growth and migration of A549 cells.Methods: Lung cancer A549 cells were irradiated with 125I seed for various times. MTT, invasion assay, and flow cytometry were used to detect the proliferation, invasion, and apoptosis of treated cells, respectively. A Nimblegen genome-wide expression profile chip was used to evaluate gene expression changes in 125I seed-treated A549 cells. Validation studies were performed using phosphorylated protein chip technology, Western blot, nude mouse tumor xenograft assay, and immunohistochemical experiments. All statistical analyses were performed using unpaired Student's t tests and Kruskal-Wallis test.Results: Irradiation with 125I seed inhibited A549 cell proliferation and invasion and induced apoptosis (primarily early apoptosis). Irradiation with 125I seed also caused the downregulation of p38MAPK, degradation of mouse double-minute 2 homolog (MDM2), and higher expression of p53, which eventually resulted in non-small cell lung cancer cell apoptosis.Conclusion:125I seed irradiation activated the p38MAPK/MDM2/p53 signaling pathway and promoted non-small cell lung cancer cell apoptosis. Future clinical studies targeting this signal may provide a new potential therapeutic approach for non-small cell lung cancer.

scholarly journals Systematic Analysis Identifies NUF2 as an Immunological and Prognostic Biomarker for Non-small cell lung cancer

2021 ◽  
Author(s):  
xia li ◽  
zhongquan yi ◽  
lianlian zhang ◽  
jin zhou ◽  
wenchun song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Functional Enrichment ◽  
Small Cell Lung ◽  
Hub Genes ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background Non-small cell lung cancer (NSCLC) is a part of the most common cancers in the world. A lot of efforts have been made to clarify the etiology of non-small cell lung cancer, but the molecular mechanism of non-small cell lung cancer is still unclear. Methods In order to identify candidate genes in the occurrence and progression of non-small cell lung cancer, GSE19804 GSE118370 GSE19188 GSE27262 and GSE33532 microarray data sets were downloaded from the Gene Expression General (GEO) database. Identify differentially expressed genes (DEGS) and perform functional enrichment analysis. The protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. A total of 562 DEGS were identified, consisting of 98 downregulated genes and 464 upregulated genes. Abundant functions and pathways of DEGS include p53 signaling pathway, Cell adhesion molecules,Leukocyte transendothelial migration,Vascular smooth muscle contraction,Complement and coagulation cascades and Axon guidance. Tumor immunity was assessed to investigate the functions of hub genes. Results Totally 562 genes were found to be dysregulated. 12 genes were considered to be the hub genes. NUF2 was considered as the potential immunotherapeutic targets with future clinical significance.12 hub genes were detected, and biological process analysis showed that these genes are mainly enriched in p53 signaling pathway,Progesterone-mediated oocyte maturation,Cell cycle, Oocyte meiosis and Cellular senescence Survival analysis shows that NUF2 may be linked to the occurrence, invasion or recurrence of non-small cell lung cancer. Conclusion NUF2 genes discovered in this study help us include the molecular mechanisms of the occurrence and progression of non-small cell lung cancer, and provide candidate targets for the diagnosis and treatment of non-small cell lung cancer.

Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

scholarly journals Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Yucui Ma ◽  
Qu Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Erk Signaling ◽  
Network Pharmacology ◽  
Protein Interaction Data ◽  
Small Cell Lung

AbstractFucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein–protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

scholarly journals ARHGAP10 inhibits the epithelial–mesenchymal transition of non-small cell lung cancer by inactivating PI3K/Akt/GSK3β signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lan-Lan Lin ◽  
Fan Yang ◽  
Dong-Huan Zhang ◽  
Cong Hu ◽  
Sheng Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Rho Gtpase ◽  
Epithelial Mesenchymal Transition ◽  
Essential Element ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Abstract Background Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial–mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Methods Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. Results ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. Conclusion ARHGAP10 inhibits the epithelial–mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.

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