scholarly journals P62.09 PLGF Regulates Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Wnt/β-catenin Pathway

2021 ◽  
Vol 16 (3) ◽  
pp. S550-S551
Author(s):  
B. Han ◽  
W. Zhang ◽  
Y. Zhang ◽  
F. Qian ◽  
W. Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Stimulation Of

scholarly journals PLGF Knockdown Attenuates Hypoxia-Induced Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Inhibiting Wnt/β-Catenin Pathway

2020 ◽  
Author(s):  
Wei Zhang ◽  
Yanwei Zhang ◽  
Wensheng Zhou ◽  
Fangfei Qian ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lactate Dehydrogenase ◽  
Growth Factor ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Placental Growth Factor ◽  
Tumor Xenografts ◽  
Hypoxia Treatment ◽  
Stimulation Of

Abstract Background: Angiogenic placental growth factor (PLGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PLGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms. Methods: PLGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PLGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PLGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed. Results: Hypoxia treatment led to up-regulation of PLGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis inH358 and H1975 cells, which were obviously reversed by knocking down PLGF. In tumors, PLGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PLGF overexpression markedly strengthened cell proliferation and glycolysis, and increased β-catenin expressionin PC9 cells, which were abrogated by XAV939. Conclusion: PLGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.

scholarly journals PlGF knockdown attenuates hypoxia-induced stimulation of cell proliferation and glycolysis of lung adenocarcinoma through inhibiting Wnt/β-catenin pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Zhang ◽  
Yanwei Zhang ◽  
Wensheng Zhou ◽  
Fangfei Qian ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lactate Dehydrogenase ◽  
Growth Factor ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Placental Growth Factor ◽  
Tumor Xenografts ◽  
Hypoxia Treatment ◽  
Stimulation Of

Abstract Background Angiogenic placental growth factor (PlGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PlGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms. Methods PlGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PlGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PlGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed. Results Hypoxia treatment led to up-regulation of PlGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis in H358 and H1975 cells, which were obviously reversed by knocking down PlGF. In tumors, PlGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PlGF overexpression markedly strengthened cell proliferation, which was inhibited by β-catenin knockdown. Consistently, XAV939, inhibitor of Wnt/β-catenin pathway, also inhibited PlGF-induced cell proliferation, glycolysis, and β-catenin expression in PC9 cells. Conclusion PlGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.

scholarly journals LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Qian ◽  
Yan Zhang ◽  
Haoming Ji ◽  
Yucheng Shen ◽  
Liangfeng Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
High Morbidity ◽  
Lipid Transfer ◽  
Protein Coding ◽  
Cell Proliferation And Migration ◽  
Reduce Cell Proliferation ◽  
And Migration ◽  
Insight Into ◽  
Proliferation And Migration

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD. Methods The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student’s t test or one-way analysis of variance. Results LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells. Conclusion LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.

scholarly journals PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

2018 ◽  
Vol 47 (5) ◽  
pp. 1909-1924 ◽  
Author(s):  
Jian Zhou ◽  
Kwang Joo Kwak ◽  
Zuoren Wu ◽  
Dawei Yang ◽  
Jing Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Membrane Potential ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Human Lung ◽  
Nsclc Patients ◽  
Gefitinib Resistance

Background/Aims: Tyrosine kinase inhibitor gefitinib significantly improves the survival of patients with non-small-cell lung cancer (NSCLC) by inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. However, patients eventually develop resistance to gefitinib through uncharacterized mechanisms. It is known that plasminogen activator urokinase receptor (PLAUR) plays an important role in cell proliferation, migration and apoptosis. However, the role of PLAUR, particularly exosomal PLAUR in gefitinib resistance in NSCLC has not been reported. The aim of this study is to determine the relationship between PLAUR and gefitinib resistance. Methods: In this study, a tethered cationic lipoplex nanoparticle (TCLN) biochip containing molecular beacons was used as probes to detect PLAUR mRNA in plasma exosomes from patients with gefitinib-sensitive and -resistant NSCLC. In vitro, Real-time PCR was used to examine the expression of PLAUR mRNA and Western blot was applied to examine the expression of related proteins. The gene knockdown was achieved by Lentivirus based RNA silence technique. The cell counting kit-8 assay and EdU incorporation were used to examine cell proliferation. The flow cytometry was applied to determine cell apoptosis and cell cycle, while the mitochondrial membrane potential was measured by JC-1 dye assay. Signaling pathway affected by PLAUR knockdown was identified by cDNA Microarray. The effect of PLAUR knockdown on tumorigenesis was analyzed in vivo. Results: We found that the exosomal PLAUR mRNA in the plasma of gefitinib-resistant NSCLC patients was significantly increased compared to that of gefitinib-sensitive NSCLC patients. The PLAUR mRNA and soluble PLAUR protein were also significantly increased in gefitinib-resistant human lung adenocarcinoma PC9R cells compared to gefitinib-sensitive PC9 cells. Silencing PLAUR in PC9R cells impaired mitochondrial membrane potential and increased cell apoptosis via EGFR/p-AKT/survivin signaling pathway. Furthermore, EGFR was upregulated in the geftinib-resistant PC9R cells, and knockdown of EGFR significantly increased cell apoptosis. Conclusions: Taken together, our results demonstrated that PLAUR induces geftinib-resistance through EGFR/p-AKT/survivin signaling pathway in gefitinib-resistant human lung adenocarcinoma cells. PLAUR could be a novel therapeutic target for gefitinib-resistant NSCLC patients.

scholarly journals Polyamine-modulated c-Myc expression in normal intestinal epithelial cells regulates p21Cip1 transcription through a proximal promoter region

2006 ◽  
Vol 398 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Lan Liu ◽  
Xin Guo ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Bernard S. Marasa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Repression ◽  
Critical Role ◽  
Ectopic Expression ◽  
Proximal Region ◽  
Proximal Promoter ◽  
Transcriptional Level ◽  
Intestinal Epithelial ◽  
Major Player ◽  
Stimulation Of

Maintenance of intestinal mucosal epithelial integrity requires cellular polyamines that regulate expression of various genes involved in cell proliferation, growth arrest and apoptosis. Our previous studies have shown that polyamines are essential for expression of the c-myc gene and that polyamine-induced c-Myc plays a critical role in stimulation of normal IEC (intestinal epithelial cell) proliferation, but the exact downstream targets of induced c-Myc are still unclear. The p21Cip1 protein is a major player in cell cycle control, which is primarily regulated at the transcriptional level. The current study was designed to determine whether induced c-Myc stimulates normal IEC proliferation by repressing p21Cip1 transcription following up-regulation of polyamines. Overexpression of the ODC (ornithine decarboxylase) gene increased levels of cellular polyamines, induced c-Myc expression and inhibited p21Cip1 transcription, as indicated by repression of p21Cip1 promoter activity and a decrease in p21Cip1 protein levels. In contrast, depletion of cellular polyamines by inhibiting ODC enzyme activity with α-difluoromethylornithine decreased c-Myc, but increased p21Cip1 transcription. Ectopic expression of wild-type c-myc not only inhibited basal levels of p21Cip1 transcription in control cells, but also prevented increased p21Cip1 in polyamine-deficient cells. Experiments using different p21Cip1 promoter mutants showed that transcriptional repression of p21Cip1 by c-Myc was mediated through Miz-1- and Sp1-binding sites within the proximal region of the p21Cip1 promoter in normal IECs. These findings confirm that p21Cip1 is one of the direct mediators of induced c-Myc following increased polyamines and that p21Cip1 repression by c-Myc is implicated in stimulation of normal IEC proliferation.

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