scholarly journals Succinate Coenzyme A Ligase Beta-Like Protein from Trichinella spiralis Suppresses the Immune Functions of Rat PBMCs in Vitro and Inhibits the Secretions of Interleukin-17 in Vivo

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 167
Author(s):  
Sun ◽  
Li ◽  
Naqvi ◽  
Naqvi ◽  
Chu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Coenzyme A ◽  
Trichinella Spiralis ◽  
No Production ◽  
Immune Functions ◽  
Partial Reaction ◽  
Coenzyme A Ligase

: Succinate Coenzyme A ligase beta-like protein (SUCLA-β) is a subunit of Succinyl-coenzyme A synthetase, which is involved in substrate synergism, unusual kinetic reaction in which the presence of SUCLA-β for one partial reaction stimulates another partial reaction. Trichinella spiralis is a parasitic nematode, which may hinder the development of autoimmune diseases. Immunomodulatory effects of SUCLA-β from Trichinella spiralis in the parasite-host interaction are unidentified. In this study the gene encoding T. spiralis SUCLA-β was cloned and expressed. Binding activities of recombinant T. spiralis SUCLA-β (rTs-SUCLA-β) to rat peripheral blood mononuclear cells (PBMCs) were checked by immunofluorescence assay (IFA) and the immuno-regulatory effects of rTs-SUCLA-β on cell migration, cell proliferation, nitric oxide (NO) production and apoptosis were observed by co-incubation of rTs-SUCLA-β with rat PBMCs in vitro, while cytokine secretions in rTs-SUCLA-β treated rats were evaluated in vivo. Furthermore, phagocytosis of monocytes was detected by flow cytometry and effects of rTs-SUCLA-β-induced protective immunity on T. spiralis adult worms and muscle larva were evaluated in rats. The IFA results revealed that rTs-SUCLA-β could bind to rat PBMCs. Treatment of PBMCs with rTs-SUCLA-β significantly decreased the monocyte phagocytosis, cell migration and cell proliferation, while NO production and apoptosis of PBMCs were unaffected. Results of the in vivo study showed that the IL-17 secretion decreased significantly after rTs-SUCLA-β administration in rats, while no significant effects were observed on the secretions of IFN-γ, IL-9, TGF-β and IL-4. Moreover, significant reduction of T. spiralis muscle larvae burden and significant increase in anti-rTs-SUCLA-β immunoglobulin level of IgG, IgG1 and IgG2a was observed in rTs-SUCLA-β-administered rats. The results indicated that rTs-SUCLA-β may be a potential target for controlling T. spiralis infection by suppressing the immune functions of the rat PBMCs and by reducing the parasite burden. Additionally it may also contribute to the treatment of autoimmune diseases and graft rejection by suppressing IL-17 immune response in the host.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

scholarly journals Pseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligase

2007 ◽  
Vol 190 (4) ◽  
pp. 1247-1255 ◽  
Author(s):  
James P. Coleman ◽  
L. Lynn Hudson ◽  
Susan L. McKnight ◽  
John M. Farrow ◽  
M. Worth Calfee ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Coenzyme A ◽  
Intercellular Signaling ◽  
Signaling Systems ◽  
Coa Ligase ◽  
Coenzyme A Ligase ◽  
Opportunistic Human Pathogen ◽  
Acyl Coenzyme A

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen which relies on several intercellular signaling systems for optimum population density-dependent regulation of virulence genes. The Pseudomonas quinolone signal (PQS) is a 3-hydroxy-4-quinolone with a 2-alkyl substitution which is synthesized by the condensation of anthranilic acid with a 3-keto-fatty acid. The pqsABCDE operon has been identified as being necessary for PQS production, and the pqsA gene encodes a predicted protein with homology to acyl coenzyme A (acyl-CoA) ligases. In order to elucidate the first step of the 4-quinolone synthesis pathway in P. aeruginosa, we have characterized the function of the pqsA gene product. Extracts prepared from Escherichia coli expressing PqsA were shown to catalyze the formation of anthraniloyl-CoA from anthranilate, ATP, and CoA. The PqsA protein was purified as a recombinant His-tagged polypeptide, and this protein was shown to have anthranilate-CoA ligase activity. The enzyme was active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate. Inhibition of PQS formation in vivo was observed for the chloro- and fluoroanthranilate derivatives, as well as for several analogs which were not PqsA enzymatic substrates. These results indicate that the PqsA protein is responsible for priming anthranilate for entry into the PQS biosynthetic pathway and that this enzyme may serve as a useful in vitro indicator for potential agents to disrupt quinolone signaling in P. aeruginosa.

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study

2017 ◽  
Vol 25 (2) ◽  
pp. 260-269 ◽  
Author(s):  
Carla R. Kruse ◽  
Mansher Singh ◽  
Stefan Targosinski ◽  
Indranil Sinha ◽  
Jens A. Sørensen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Viability ◽  
Wound Closure ◽  
In Vivo Study ◽  
Effect Of Ph

scholarly journals Apigenin Protects the Brain against Ischemia/Reperfusion Injury via Caveolin-1/VEGF In Vitro and In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Qiongyi Pang ◽  
Yun Zhao ◽  
Xiang Chen ◽  
Kaiyi Zhao ◽  
Qiongxiang Zhai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Caveolin 1 ◽  
The Brain

Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.

scholarly journals Ribophorin II promotes cell proliferation, migration, and invasion in esophageal cancer cells in vitro and in vivo

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yongshun Li ◽  
Changrong Huang ◽  
Qizhou Bai ◽  
Jun Yu
Keyword(s):  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissues ◽  
Esophageal Cancer Cells ◽  
E Cadherin

AbstractEsophageal cancer is a common digestive tract cancer, which is a serious threat to human health. Ribophorin II (RPN2) is a part of an N-oligosaccharyltransferase complex, which is excessively expressed in many kinds of cancers. In the present study, we explore the biological role of RNP2 in esophageal cancer. First, we found that the expression of RPN2 was higher in esophageal cancer tissues than in adjacent non-tumor tissues, and negatively correlated with E-cadherin expression. RPN2 expression levels in esophageal cancer tissues were positively associated with differentiation and tumor node metastasis (TNM) stage. Furthermore, the expression of RPN2 was increased significantly in esophageal cancer cell lines compared with normal cells. The effect of RPN2 down-regulation on cell proliferation, cell migration, and cell invasion was examined by cell counting kit-8 (CCK8), wound healing assay, and Transwell assay, respectively. Silencing RPN2 effectively inhibited cell proliferation of esophageal cancer cells in vitro and in vivo. Cell migration and invasion were also weakened dramatically by siRPN2 treatment of esophageal cancer cells. In addition, protein expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP-2), and E-cadherin in esophageal cancer cells was determined by Western blot analysis. PCNA, MMP-2, E-cadherin, Snail and phosphorylation-Smad2/3 expression was also regulated notably by siRPN2 treatment. These findings indicate that RPN2 exhibits oncogenetic capabilities in esophageal cancer, which could provide novel insights into esophageal cancer prevention and treatment.

scholarly journals The Long Intergenic Noncoding RNA 00707 Promotes Lung Adenocarcinoma Cell Proliferation and Migration by Regulating Cdc42

2018 ◽  
Vol 45 (4) ◽  
pp. 1566-1580 ◽  
Author(s):  
Tianshi Ma ◽  
Hongwei Ma ◽  
Zigui Zou ◽  
Xuezhi He ◽  
Yanhua Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Lung Adenocarcinoma ◽  
Microarray Analysis ◽  
Noncoding Rna ◽  
Target Gene ◽  
Qrt Pcr ◽  
Long Intergenic Noncoding Rna

Background/Aims: Lung cancer (LC) is a serious disease with high morbidity and mortality. Long noncoding RNAs (lncRNAs) have garnered attention because they participate in diverse human disorders, including cancer. Our study examined the long intergenic noncoding RNA 00707 (LINC00707). The effects of LINC00707 on lung adenocarcinoma (LAD) and molecular mechanisms are unclear. This study is aimed to investigate the role of LINC00707 in the malignant processes of LAD. Methods: Quantitative reverse transcription PCR (qRT-PCR) was used to examine the expression level of LINC00707 in tissues and cell lines. The association of LINC00707 expression and postoperative prognosis was analyzed by the Kaplan-Meier method and log-rank test. Cell proliferation was evaluated in vitro and in vivo. Transwell assays were performed to examine cell migration. Cell cycle and apoptosis was determined by flow -cytometric and western blot analyses. Microarray analysis was conducted to screen for the downstream target gene Cdc42 of LINC00707, which was identified by qRT-PCR, functional analysis, and rescue experiment. Results: The expression level of LINC00707 was clearly upregulated in LAD tissues compared to that in corresponding normal tissues. Its overexpression was related to advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis. Functional assays revealed that LINC00707 knockdown repressed LAD cell proliferation both in vitro and in vivo. This process may involve the inducing of G1 arrest and apoptosis. Moreover, cell migration was impaired after LINC00707 inhibition. Microarray analysis and rescue assays suggested that Cdc42 is an important target gene involved in the carcinogenesis of LINC00707. Conclusions: In summary, LINC00707 is a noncoding oncogene that exerts important regulatory functions in LAD, suggesting its potential as a biomarker in the prognosis and treatment of LAD.

scholarly journals TPPP3 Promotes Cell Proliferation, Invasion and Tumor Metastasis via STAT3/ Twist1 Pathway in Non-Small-Cell Lung Carcinoma

2018 ◽  
Vol 50 (5) ◽  
pp. 2004-2016 ◽  
Author(s):  
Yintao Li ◽  
Menglin Bai ◽  
Yali Xu ◽  
Weiwei Zhao ◽  
Naijia Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Metastasis ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Background/Aims: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis. Methods: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo. Results: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS). Conclusion: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.

Antimigratory and antimetastatic effect of heparin-derived 4–18 unit oligosaccharides in a preclinical human melanoma metastasis model

2009 ◽  
Vol 102 (12) ◽  
pp. 1265-1273 ◽  
Author(s):  
István Kenessey ◽  
Erika Simon ◽  
Krisztina Futosi ◽  
Bíborka Bereczky ◽  
Andrea Kiss ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Human Melanoma ◽  
Migration And Invasion ◽  
Melanoma Metastasis ◽  
Metastasis Model

SummaryHeparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect.These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.

scholarly journals MEX3A contributes to development and progression of glioma through regulating cell proliferation and cell migration and targeting CCL2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chao Yang ◽  
Haoqiang Zhan ◽  
Yiqing Zhao ◽  
Yasong Wu ◽  
Lisha Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Therapeutic Target ◽  
Malignant Tumors ◽  
Tumor Promoter ◽  
Mechanistic Study ◽  
High Morbidity ◽  
Loss Of Function

AbstractGlioma is one of the most commonly diagnosed intracranial malignant tumors with extremely high morbidity and mortality, whose treatment was seriously limited because of the unclear molecular mechanism. In this study, in order to identify a novel therapeutic target for glioma treatment, we explored the functions and mechanism of MEX3A in regulating glioma. The immunohistochemical staining of MEX3A in glioma and normal tissues revealed the upregulation of MEX3A and further indicated the relationship between high MEX3A expression and higher malignancy as well as poorer prognosis of glioma. In vitro loss-of-function and gain-of-function experiments comprehensively demonstrated that MEX3A may promote glioma development through regulating cell proliferation, cell apoptosis, cell cycle, and cell migration. In vivo experiments also suggested the inhibition of glioma growth by MEX3A knockdown. Moreover, our mechanistic study identifies CCL2 as a potential downstream target of MEX3A, which possesses similar regulatory effects on glioma development with MEX3A and could attenuate the promotion of glioma induced by MEX3A overexpression. Overall, MEX3A was identified as a potential tumor promoter in glioma development and therapeutic target in glioma treatment.

scholarly journals IFN-g-induced Jmjd3-Zeb1 axis contributes to an aggressive phenotype in lung adenocarcinoma

2020 ◽  
Author(s):  
Jianjian Yang ◽  
Xue Wang ◽  
Bing Huang ◽  
Rong Liu ◽  
Hui Xiong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Ifn Γ ◽  
Zeb1 Expression

Abstract Background Active IFN-γ signaling is a common feature of tumors responding to PD-1 checkpoint blockade. IFN-γ exhibits both anti- and pro-tumor activities. Therefore, identifying the pro-tumor effects of IFN-γ and their underlying molecular mechanisms could be a critical step for developing therapeutic strategies to maximize the anti-tumor efficacy of immunotherapies. Methods Western blot, immunofluorescence, and quantitative real-time PCR assays were used to evaluate the expression of ZEB1 and EMT associated biomarkers. Trans-well assay was used to examine the role of IFN-γ on cancer cell migration in vitro. Murine tumor xenograft models were performed to examine the effect of IFN-γ on cancer cell metastasis in vivo. Colony formation assay was performed to detect the role of ZEB1 in cell proliferation. RNA-seq was performed to analyze the EMT-associated gene expression patterns in response to IFN-g treatment. Loss-of-function analysis and chromatin immunoprecipitation were used to reveal the mechanism underlying ZEB1 induction by IFN-γ. Results we demonstrate that the treatment of lung adenocarcinoma cells with IFN-γ leads to a rapid increase of ZEB1 expression and a significant change in epithelial-mesenchymal-transition (EMT)-associated gene expression patterns. Moreover, functional analysis shows that IFN-γ promotes cell migration in vitro and metastasis in vivo. Mechanistically, IFN-γ-induced JMJD3 significantly reduces H3K27 trimethylation in the promoter of the ZEB1 gene, thereby activating ZEB1 transcription. Inhibition of JMJD3 abrogates IFN-γ-induced ZEB1 expression. We previously demonstrated that IFN-γ-mediated anti-tumor response, including suppression of cell proliferation and induction of CXCL9 and CXCL10 expression, is STAT1-IRF1 dependent. The knockdown of ZEB1 diminishes IFN-γ-mediated cell migration and metastasis, but it does not affect STAT1 and IRF1 expression and has no effect on cell proliferation as well as the induction of CXCL9 and CXCL10 expression. Conclusion Inhibition or downregulation of ZEB1 may prevent the pro-tumor activity of IFN-γ while retaining its anti-tumor function. The study expands our understanding of IFN-γ-mediated signaling and helps to identify therapeutic targets to improve current immunotherapies.

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