MiR-189 Exerts Anticancer Activity Through Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) Pathway in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 (12) ◽  
pp. 2421-2426
Author(s):  
Hongyun Ji ◽  
Hui Lu ◽  
Feng Li ◽  
Ying Qu ◽  
Qing Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Janus Kinase ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Stat3 Signaling ◽  
Induced Apoptosis

Non-small cell lung cancer (NSCLC) remains a threat to human health but its etiology remains unclear. MicroRNAs (miRNAs) are involved in NSCLC progression. This study aims to elucidate the mechanism by how exosomal miR-189 functions in NSCLC. After identification, BMSCs were co-cultured with NSCLC cells which were then transfected with miR-189 mimics followed by analysis of the expression of JAK2/Stat3 proteins and miR-189, cell migration and invasion by Transwell assay, cell viability by MTT assay, apoptosis by flow cytometry. miR-189 is downregulated in NSCLC cells and tissues. miR-189 overexpression inhibited the phosphorylation of JAK2/Stat3 and suppressed malignant characteristics of cancer cells and induced apoptosis. Co-culture with BMSCs and NSCLC cells elevated miR-189 level and inactivated JAK2/STAT3 signaling, thereby suppressing malignant characteristics of cancer cells. In conclusion, BMSCs carrying miR-189 restrain NSCLC progression by blocking JAK2/STAT3 signaling, which may help development of gene therapy for NSCLC.

scholarly journals N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5

2018 ◽  
Vol 45 (5) ◽  
pp. 2054-2070 ◽  
Author(s):  
Ye Liang ◽  
Wenhua Xu ◽  
Shihai Liu ◽  
Jingwei Chi ◽  
Jisheng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Sodium Dodecyl ◽  
Death Receptor ◽  
Small Cell ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Induced Apoptosis

Background/Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. Methods: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. Results: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. Conclusion: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

scholarly journals Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhiqiang Wu ◽  
Bin Xu ◽  
Zhiyi Yu ◽  
Qin He ◽  
Zhuyuan Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathways ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stat3 Signaling ◽  
Induced Apoptosis ◽  
Gefitinib Resistance

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.

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