scholarly journals Heterogeneous Nuclear Ribonucleoprotein A1 Loads Batched Tumor-Promoting MicroRNAs Into Small Extracellular Vesicles With the Assist of Caveolin-1 in A549 Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yangyang Li ◽  
Jian Zhang ◽  
Sha Li ◽  
Chongye Guo ◽  
Qian Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
A549 Cells ◽  
Extracellular Vesicle ◽  
Small Rna Sequencing ◽  
Nsclc Cell Line ◽  
Caveolin 1 ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
And Migration ◽  
Nuclear Ribonucleoprotein

MicroRNAs in small extracellular vesicle (sEV-miRNAs) have been widely investigated as crucial regulated molecules secreted by tumor cells to communicate with surroundings. It is of great significance to explore the loading mechanism of sEV-miRNAs by tumor cells. Here, we comprehensively illustrated a reasoned loading pathway of batched tumor-promoting sEV-miRNAs in non-small cell lung cancer (NSCLC) cell line A549 with the application of a multi-omics method. The protein heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was strictly selected as a powerful sEV-miRNA loading protein from miRNA-binding proteome and further verified through small RNA sequencing after hnRNPA1 silence. In terms of the mechanism, SUMOylated hnRNPA1 in sEVs was verified to control sEV-miRNA loading. Subsequently, as a scaffolding component of caveolae, caveolin-1 (CAV1) was detailedly demonstrated to assist the loading of SUMOylated hnRNPA1 and its binding miRNAs into sEVs. Inhibition of CAV1 significantly prevented SUMOylated hnRNPA1 from encapsulating into sEVs, resulting in less enrichment of sEV-miRNAs it loaded. Finally, we confirmed that hnRNPA1-loaded sEV-miRNAs could facilitate tumor proliferation and migration based on database analysis and cytological experiments. Our findings reveal a loading mechanism of batched tumor-promoting sEV-miRNAs, which may contribute to the selection of therapeutic targets for lung cancer.

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC

2018 ◽  
Vol 26 (4) ◽  
pp. 519-528 ◽  
Author(s):  
Dong Yang ◽  
Jian-Jun Wang ◽  
Jin-Song Li ◽  
Qian-Yu Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Size ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Invasion And Migration ◽  
Metastatic Capacity ◽  
And Migration

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently been identified to be associated with metastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism are unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume, and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death in A549 cells. Furthermore, miR-103 decreased the invasion and migration abilities in A549 cells, as evidenced by Transwell and wound healing results. Downregulation of miR-103 significantly reduced the level of programmed cell death 10 (PDCD10). We found a significant decrease in the relative luciferase activity of the reporter gene in A549 cells cotransfected with the miR-103 mimic and pGL3-PDCD10 WT 3′-UTR, but not pGL3-PDCD10 mut 3′-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased apoptosis, and decreased invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of the miR-103/PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

scholarly journals Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK-Dependent NLRP3 Inflammasome Regulation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Weidong Ma ◽  
Ziyuan Wang ◽  
Yan Zhao ◽  
Qibin Wang ◽  
Yonghong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nlrp3 Inflammasome ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Human Lung Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.

Gene expression profiling after LINC00472 overexpression in an NSCLC cell line

2021 ◽  
pp. 1-14
Author(s):  
Danbi Seo ◽  
Jungwook Roh ◽  
Yeonsoo Chae ◽  
Wanyeon Kim
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Tumor Suppressors ◽  
Enrichment Analysis ◽  
Nsclc Cell Line ◽  
Sequencing Analysis ◽  
Genetic Characteristics ◽  
Migration Assay ◽  
Non Coding Rna ◽  
And Migration

Lung cancer accounts for a large proportion of cancer-related deaths worldwide. Personalized therapeutic medicine based on the genetic characteristics of non-small cell lung cancer (NSCLC) is a promising field, and discovering clinically applicable biomarkers of NSCLC is required. LINC00472 is a long non-coding RNA and has been recently suggested to be a biomarker of NSCLC, but little is known of its mechanism in NSCLC. Thus, the current study was performed to document changes in gene expression after LINC00472 overexpression in NSCLC cells. As a result of cell viability and migration assay, LINC00472 downregulated cell survival, proliferation, and motility. Transcriptome sequencing analysis showed 3,782 genes expression were changed in LINC00472 overexpressing cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed most genes were associated with intracellular metabolism. The PPP1R12B, RGS5, RBM5, RBL2, LDLR and PTPRM genes were upregulated by LINC00472 overexpression and these genes functioned as tumor suppressors in several cancers. In contrast, SPSB1, PCNA, CD24, CDK5, CDC25A, and EIF4EBP1 were downregulated by LINC00472, and they functioned as oncogenes in various cancers. Consequently, the function of LINC00472 in tumorigenesis might be related to changes in the expressions of other oncogenes and tumor suppressors.

Role of DACH1 on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Junjie Yu ◽  
Ping Jiang ◽  
Ke Zhao ◽  
Zhiguo Chen ◽  
Tao Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Objective: To investigate DACH1 protein expression in lung cancer tissue and matched paracancerous tissue, and explore its effect on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells (HLACs). Methods: Tumor tissue and matched paracancerous tissue was collected from 46 patients with pathologically diagnosed lung cancer. RT-PCR was perfomed to detect DACH1 mRNA expression and immunohistochemistry to measured DACH1 protein expression. To determine the effect of DACH1 on lung cancer behavior, small interfering RNA (siRNA) was used to silence DACH1 expression in A549 cells. The impact on the proliferation of tumor cells was then observed by MTT assay, changes in the invasion of tumor cells were identified using transwell chamber assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression of DACH1 mRNA and DACH1 protein were significantly decreased in lung cancer tissue versus matched paracancerous control tissue. Silencing of DACH1 expression in A549 cells significantly enhanced cell proliferation, significantly increased cell invasion and significantly reduced spontaneous apoptosis. Conclusion: DACH1 is downregulated in lung adenocarcinoma tissue. In vitro assessment shows that DACH1 functions as a tumor suppressor, suggesting its potential use as new target for lung cancer treatment.

scholarly journals Contribution of Neuropilin-1 in Radiation-Survived Subclones of NSCLC Cell Line H1299

2021 ◽  
Vol 43 (3) ◽  
pp. 1203-1211
Author(s):  
Kaori Tsutsumi ◽  
Ayaka Chiba ◽  
Yuta Tadaki ◽  
Shima Minaki ◽  
Takahito Ooshima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Motility ◽  
Cell Line ◽  
Tumor Cells ◽  
Tube Formation ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Migration Assay ◽  
Lung Cancer Patients ◽  
Neuropilin 1

Non-small cell lung cancer (NSCLC) is an aggressive lung cancer accounting for approximately 85% of all lung cancer patients. For the patients with Stages IIIA, IIIB, and IIIC, the 5-year survival is low though with the combination with radiotherapy and chemotherapy. In addition, the occurrence of tumor cells (repopulated tumors) that survive irradiation remains a challenge. In our previous report, we subcloned the radiation-surviving tumor cells (IR cells) using the human NSCLC cell line, H1299, and found that the expression of neuropilin-1 (NRP-1) was upregulated in IR cells by the microarray analysis. Here, we investigated the contribution of neuropilin-1 to changes in the characteristics of IR cells. Although there were no differences in angiogenic activity in the tube formation assay between parental and IR cells, the cell motility was increased in IR cells compared to parental cells in the cell migration assay. This enhanced cell motility was suppressed by pretreatment with anti-NRP-1 antibody. Although further studies are necessary to identify other molecules associated with NRP-1, the increase in cellular motility in IR cells might be due to the contribution of NRP-1. Inhibition of NRP-1 would help control tumor malignancy in radiation-surviving NSCLC.

Effects of Intermittent Cisplatin Intervention on 6PGD Levels and Tumor Growth and Migration in A549 Lung Cancer Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
WU Qiang ◽  
TANG Lin-dong ◽  
WU Yan-hui ◽  
LI Qiang ◽  
YU Li
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration Ability ◽  
Western Blot Method ◽  
And Migration ◽  
A549 Lung

Aim: To investigate the changes of A549 protein 6PGD expression, tumor growth and migration, NADPH and ROS levels in lung cancer cells after intermittent intervention with DDP. Methods: The sensitivity of A549 cells to DDP was detected by cck-8 method, A549 cells were treated by DDP intermitten, 6PGD protein expression was detected by Western blot method, and the ROS level of A549 cells was determined by ROS kit. NADPH levels of A549 cells were determined by NADPH kit. Result: After DDP intermittent intervention, the expression of 6PGD protein in lung cancer cells A549 was increased, the growth and migration of A549 cells were significantly inhibited, and ROS and NADPH levels were significantly increased. Conclusion: 6PGD were upregulated in after DDP intermittent intervention and affected the migration ability in lung cancer cells.

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