scholarly journals LMP1‐positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling

2019 ◽  
Vol 8 (13) ◽  
pp. 6082-6094 ◽  
Author(s):  
Zhibao Zhang ◽  
Xuehui Yu ◽  
Zhuan Zhou ◽  
Bo Li ◽  
Jinwu Peng ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
P38 Mapk ◽  
Extracellular Vesicles ◽  
Mapk Signaling ◽  
Carcinoma Cells

scholarly journals Tumor-derived extracellular vesicles inhibit HGF/c-Met and EGF/EGFR pathways to accelerate the radiosensitivity of nasopharyngeal carcinoma cells via microRNA-142-5p delivery

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Changyu Zhu ◽  
Xiaolei Jiang ◽  
Hua Xiao ◽  
Jianmei Guan
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Extracellular Vesicles ◽  
Nude Mice ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Expression Patterns ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Relationship Of ◽  
Dual Luciferase Reporter Assay

AbstractRadioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

scholarly journals microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

2021 ◽  
Vol 12 ◽  
pp. 204173142110216
Author(s):  
Shaoqian Cui ◽  
Lei Zhang
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Disc Degeneration ◽  
Extracellular Vesicles ◽  
Intervertebral Disc Degeneration ◽  
Mapk Signaling ◽  
Ecm Degradation

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been reported to deliver exogenous microRNAs (miRNAs or miRs) to reduce the progression of intervertebral disc degeneration (IDD). The purpose of the current study was to investigate the therapeutic potential of MSC-derived EVs delivering miR-129-5p in IDD. First, miR-129-5p expression levels were quantified in nucleus pulposus (NP) tissues of IDD patients. An IL-1β-induced NP cell model with IDD was then established, and co-cultured with EVs derived from MSCs that had been transfected with miR-129-5p mimic or inhibitor to elucidate the effects of miR-129-5p on cell viability, apoptosis, and ECM degradation. In addition, RAW264.7 cells were treated with the conditioned medium (CM) of NP cells. Next, the expression patterns of polarization markers and those of inflammatory factors in macrophages were detected using flow cytometry and ELISA, respectively. Lastly, rat models of IDD were established to validate the in vitro findings. It was found that miR-129-5p was poorly-expressed in NP tissues following IDD. Delivery of miR-129-5p to NP cells by MSC-derived EVs brought about a decrease in NP cell apoptosis, ECM degradation and M1 polarization of macrophages. Moreover, miR-129-5p directly-targeted LRG1, which subsequently promoted the activation of p38 MAPK signaling pathway, thus polarizing macrophages toward the M1 phenotype. Furthermore, MSC-derived EVs transferring miR-129-5p relieved IDD via inhibition of the LRG1/p38 MAPK signaling in vivo. Altogether, our findings indicated that MSC-derived EVs carrying miR-129-5p confer protection against IDD by targeting LRG1 and suppressing the p38 MAPK signaling pathway, offering a novel theranostic marker in IDD.

S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway

2016 ◽  
Vol 56 (3) ◽  
pp. 972-984 ◽  
Author(s):  
Anchuan Li ◽  
Dingbo Shi ◽  
Benhua Xu ◽  
Jingshu Wang ◽  
Yan-Lai Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Human Nasopharyngeal Carcinoma

scholarly journals Maslinic acid activates mitochondria-dependent apoptotic pathway in cardiac carcinoma

2014 ◽  
Vol 37 (4) ◽  
pp. 217 ◽  
Author(s):  
Tingmin Chang ◽  
Xiumin Li ◽  
Xiangyu Chen ◽  
Lili Zhang ◽  
Fang Yang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Natural Compound ◽  
Mapk Signaling ◽  
Carcinoma Cells ◽  
Tumor Xenograft ◽  
Dependent Manner ◽  
Maslinic Acid ◽  
Limited Effectiveness ◽  
Wide Range ◽  
Cardiac Carcinoma

Purpose: Cardiac carcinoma is the most common subtype of gastric cancer and its incidence has increased in recent years. The current chemotherapeutic drugs exhibit limited effectiveness and significant side effects in patients. Maslinic acid (MA) exerts an anti-tumor activity on a wide range of cancers and has no significant side effect; however, the anti-tumor effect of MA on cardiac carcinoma has not yet been explored. Methods: MTT assays, tumor xenograft animal model, immunoblotting, MMP assessment and flow cytometry were performed in this study. Results: MA was able to suppress the viability of cardiac carcinoma cells in both a time- and dose-dependent manner. This natural compound exhibited no cytotoxicity in normal cells. Its inhibitory effect on tumor growth was further confirmed in a mouse model. Mechanistically, MA induced the activation of p38 MAPK in cardiac carcinoma cells and, in turn, changed their mitochondrial membrane potential (MMP). Finally, caspase cascades were activated by a series of cleavages, leading to apoptosis in cardiac cancer cells. Inhibition of p38 MAPK signaling was able to rescue the effect of MA on cardiac carcinoma cells. Conclusion: Our data demonstrated that natural compound, MA, suppressed the growth of cardiac carcinoma by inducing apoptosis via the p38 MAPK/mitochondria/caspase pathway. MA and its derivatives may be promising anti-tumor agents for cardiac carcinoma treatment in the future. (Supplemental Figures available here.)

scholarly journals S100A8/A9 Molecular Complexes Promote Cancer Migration and Invasion via the p38 MAPK Pathway in Nasopharyngeal Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ning Xu ◽  
Bei-Bei Zhang ◽  
Xia-Ning Huang ◽  
Xiang Yi ◽  
Xue-Min Yan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Molecular Complexes ◽  
Mapk Signaling ◽  
Inflammatory Factors ◽  
Migration And Invasion ◽  
Cancer Migration ◽  
P38 Mapk Pathway ◽  
Associated Proteins

Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by the Mann–Whitney U test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g., MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via the p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.

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