scholarly journals Knockdown of CENPF Inhibits the Progression of Lung Adenocarcinoma Mediated by ERβ2/5 Pathway

2020 ◽  
Author(s):  
Hexiao Tang ◽  
Yuquan Bai ◽  
Lecai Xiong ◽  
Yanhong Wei ◽  
Weidong Hu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Biological Effects ◽  
Nuclear Proteins ◽  
Signal Transduction Pathways ◽  
Database Analysis ◽  
Gene Pathway ◽  
Human Centromere ◽  
Adenocarcinoma Of Lung ◽  
Beta 2 ◽  
Geo Database

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

scholarly journals Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-26 ◽  
Author(s):  
Chen-Yi Liao ◽  
Ching-Chang Lee ◽  
Chi-chang Tsai ◽  
Chao-Wen Hsueh ◽  
Chih-Chiang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Natural Products ◽  
Multidrug Resistance ◽  
Intracellular Signaling ◽  
Poor Prognosis ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Chemopreventive Agents ◽  
Intracellular Signaling Pathways ◽  
Anticancer Effects

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes

1990 ◽  
Vol 10 (10) ◽  
pp. 5486-5495
Author(s):  
L R Gottschalk ◽  
J M Leiden
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Binding Sites ◽  
Cell Receptor ◽  
Nuclear Proteins ◽  
Transcriptional Enhancer ◽  
Enhancer Element ◽  
Beta 2 ◽  
Beta Gene

A transcriptional enhancer has been mapped to a region 5.5 kilobases 3' of the C beta 2 gene in the human T-cell receptor (TCR) beta-chain locus. Transient transfections allowed localization of enhancer activity to a 480-base-pair HincII-XbaI restriction enzyme fragment. The TCR beta enhancer was active on both the minimal simian virus 40 promoter and a TCR beta variable gene promoter in both TCR alpha/beta + and TCR gamma/delta + T cells. It displayed significantly less activity in Epstein-Barr virus-transformed B cells and K562 chronic myelogenous leukemia cells and no activity in HeLa fibroblasts. DNA sequence analysis revealed that the enhancer contains a consensus immunoglobulin kappa E2 motif, as well as an AP-1-binding site and a cyclic AMP response element. DNase I footprint analyses using Jurkat T-cell nuclear extracts allowed the identification of five nuclear protein-binding sites, T beta 1 to T beta 5, within the enhancer element. Deletion and in vitro mutagenesis studies demonstrated that the T beta 2- and T beta 3- and T beta 4-binding sites are each required for full transcriptional enhancer activity. In contrast, deletion of the T beta 1- and T beta 5-binding sites had essentially no effect on enhancer function. Electrophoretic mobility shift assays demonstrated that TCR alpha/beta + and TCR gamma/delta + T cells expressed T beta 2-, T beta 3-, and T beta 4-binding activities. In contrast, non-T-cell lines, in which the enhancer was inactive, each lacked expression of at least one of these binding activities. TCR alpha and beta gene expression may be regulated by a common set of T-cell nuclear proteins in that the T beta 2 element binding a set of cyclic AMP response element-binding proteins that are also bound by the T alpha 1 element of the human TCR alpha enhancer and the decamer element present in a large number of human and murine TCR beta promoters. Similarly, the T beta 5 TCR beta-enhancer element and the T alpha 2 TCR alpha-enhancer element bind at least one common T-cell nuclear protein. Taken together, these results suggest that TCR beta gene expression is regulated by the interaction of multiple T cell nuclear proteins with a transcriptional enhancer element located 3' of the C beta 2 gene and that some of these proteins may be involved in the coordinate regulation of TCR alpha and beta gene expression.

scholarly journals Acute myeloid leukaemia expressing the leucocyte integrin CD11b - a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis

1998 ◽  
Vol 100 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Elisabeth Paietta ◽  
Janet Andersen ◽  
Jorge Yunis ◽  
Jacob M. Rowe ◽  
Peter A. Cassileth ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Prognosis ◽  
Database Analysis ◽  
Acute Myeloid

scholarly journals Four Key Genes are Biomarkers Associated with Immunity in Neuroglioma

2020 ◽  
Author(s):  
Xin Yang ◽  
Jia-Qi Hao ◽  
Yu Zhang ◽  
Jia-Ying Shi ◽  
Xiao-Lin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Intracranial Tumor ◽  
Ppi Networks ◽  
Key Genes ◽  
The Relationship ◽  
Geo Database ◽  
Differential Genes

Abstract Background: Glioma is the most common intracranial tumor, with glioblastoma being the most malignant. However, its treatment is very few, and targeted therapy is an important breakthrough in treatment. Methods: Numerous genes are differentially expressed during the progression of glioma, some of which may play a key role. To find key genes, we analyzed three multi-sample microarrays (GSE4290, GSE54004, and GSE29796) in the GEO database to obtain intersection differential genes among them. We entered all DEGs into the STRING database and characterized the protein interactions of these DEGs as visual PPI networks by Cytoscape software. Also, we used the GEPIA2 and CGGAdatabase to predict the relationship between key genes and the prognosis of glioma patients.Results: A total of 222 up-regulated genes and 127 down-regulated genes were identified. Four genes(FN1, LAMB1, FAM20C, and COL6A1) were significantly negatively correlated with malignant glioma survival. Expression levels of four genes increased with the glioma grade. All gene expression is more common in IDH wild glioma and are enriched in the Mesenchymal subtype(AUC>0.8). In addition,they can be defined as hazard factors for glioma. We found that these genes were co-expressed and jointly involved in the infiltration of immune cells in tumors. Conclusion: In conclusion, FN1, LAMB1, FAM20C, and COL6A1 is associated with poor prognosis in glioma patients. These genes might be clinical targets of glioma immunotherapy.

miR-628-5p promotes growth and migration of osteosarcoma by targeting IFI44L

2020 ◽  
Vol 98 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Ju-Yong Wang ◽  
Ju-Qiang Wang ◽  
Shi-Bao Lu
Keyword(s):  
Untranslated Region ◽  
Poor Prognosis ◽  
Luciferase Activity ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Activity Assay ◽  
Luciferase Activity Assay ◽  
And Migration ◽  
Geo Database

This study investigated the role of miR-628-5p and interferon-induced protein 44-like (IFI44L) in osteosarcoma (OS) and determined whether miR-628-5p modulated OS growth by regulating IFI44L. Based on the data downloaded from Gene Expression Omnibus (GEO) database, we revealed that the expression of IFI44L was downregulated in OS and low expression of IFI44L was correlated with better prognosis of patients with OS. Biological prediction of its upstream regulatory miRNAs on the miRWalk website found that miR-628-5p is a possible upstream regulatory miRNA of IFI44L. Luciferase activity assay demonstrated that miR-628-5p could bind to the 3′ untranslated region (UTR) of IFI44L, which proved the above prediction. The expression of miR-628-5p is upregulated in OS and high expression of miR-628-5p is correlated with poor prognosis of patients with OS. The results of RT-qPCR showed that the expression of miR-628-5p in MG-63, U2OS, Saos-2, and SW1353 cells was significantly higher than that in the hFOB1.19 cells. Downregulation of miR-628-5p by miR-628-5p inhibitor significantly inhibited the proliferation, migration, and invasion of MG-63 cells. By rescue assay, we found that knockdown of IFI44L rescued the proliferation and motility of miR-628-5p depleted MG-63 cells. Collectively, our present data illustrated that miR-628-5p promoted the growth and motility of OS at least partly by targeting IFI44L. Moreover, miR-628-5p and IFI44L might be proposed as promising biomarkers in OS diagnosis and treatment.

scholarly journals MAP kinase phosphatase 1: a novel mediator of biological effects of glucocorticoids?

2003 ◽  
Vol 178 (1) ◽  
pp. 5-12 ◽  
Author(s):  
AR Clark
Keyword(s):  
Map Kinase ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Negative Regulator ◽  
Signal Transduction Pathways ◽  
Therapeutic Effects ◽  
Inflammatory Gene Expression ◽  
Map Kinase Phosphatase ◽  
Mapk Phosphatase ◽  
Synthetic Glucocorticoids

Synthetic glucocorticoids (GCs) potently inhibit the expression of pro-inflammatory genes and are widely used in the treatment of inflammatory diseases. However, some patients are resistant to the therapeutic effects of GCs, and many suffer deleterious side effects from these drugs. Furthermore, the precise mechanisms by which GCs inhibit pro-inflammatory gene expression remain unclear. A number of recent papers report that GCs induce the sustained expression of MAP kinase (MAPK) phosphatase 1 (MKP-1), a negative regulator of MAPK signal transduction pathways. The potential relevance of MKP-1 to some of the biological effects of GCs is discussed.

Racial disparities in survival of adult T-cell leukemia/lymphoma patients in the United States: A SEER database analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16503-e16503
Author(s):  
Renju V. Raj ◽  
Sanjib Basu ◽  
Lisa N Boggio ◽  
Henry C. Fung ◽  
Stephanie A. Gregory ◽  
...  
Keyword(s):  
United States ◽  
T Cell ◽  
Poor Prognosis ◽  
The United States ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Database Analysis ◽  
Adult T Cell Leukemia ◽  
Age Of Diagnosis ◽  
Rare Malignancy

e16503 Background: Adult T cell Leukemia/Lymphoma (ATL) is an aggressive lymphoproliferative disorder etiologically linked to Human T cell Lymphotropic Virus -1 (HTLV-1). HTLV-1 infection is endemic in areas of Japan, the Caribbean, South America, and Africa. ATL runs a very aggressive clinical course. It is a rare malignancy in the United States (US), and epidemiologic data are limited. We undertook a Surveillance Epidemiology and End Results (SEER) based database analysis to identify survival data of ATL patients (pts) with emphasis on race and ethnicity. Methods: We used the SEER 17 Registry data (1973-2008) for pts with a confirmed diagnosis of ATL. ICD-O-3 code 9827/3 was used to identify pts with ATL. The following exclusion criteria were used: diagnosis at death certificate or autopsy, no follow-up records, diagnosis of second malignancies or lack of documentation of sex or age at diagnosis. The Kaplan Meier method was used to evaluate survival in different races. Statistical tests were done utilizing R statistical software. Results: 272 patients were included in the final analysis (126 females; 146 males). Pts were stratified by race: White (155), Black (80), Other (33), Unknown (4). Median age (yr) of diagnosis in Blacks (51.5) was lower than in Whites (65) and other races (65). Average age of diagnosis in Blacks was significantly lower compared to Whites (p=0.002) and non-Blacks (p=0.0008). Survival analysis of the study group showed a median overall survival (OS) of 13 mo (95%CI 10-16). Whites had a higher median OS (21 mo) compared to blacks (5 mo); the difference in survival was strongly significant (Log-rank p-value < 0.001). Differences in survival between blacks or whites compared to other ethnic and unknown racial groups (n=37) were not statistically significant. Conclusions: ATL is a rare malignancy with poor prognosis in the US. Epidemiologic data on survival are limited. Blacks tend to have an earlier onset of disease and a poor prognosis compared to whites. The reasons for this aggressive course and earlier age of diagnosis in blacks are unknown.

Overexpression of C1QTNF6 Predicts a Poor Prognosis in Bladder Cancer

2020 ◽  
Author(s):  
Xin Zhu ◽  
Hang Tong ◽  
Shun Gao ◽  
Hubin Yin ◽  
Gongmin Zhu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Underlying Mechanism ◽  
High Expression ◽  
Migration And Invasion ◽  
Bladder Cell ◽  
Normal Bladder ◽  
Bladder Cancer Cells ◽  
Geo Database

Abstract Background: Bladder cancer is one of the most common urinary cancer. This study aimed to provide promising molecular biomarkers for bladder cancer by investigating the correlations between C1QTNF6 expressions and clinical characteristics as well as prognosis in patients with bladder cancer.Methods: C1QTNF6 RNA sequencing profiles of bladder cancer patients were collected to evaluate different expressions between normal bladder mucosa and bladder cancer from TCGA database and GEO database. The associations between C1QTNF6 expression and clinical characteristics as well as prognosis were evaluated by two independent cohorts. The cell expression of C1QTNF6 expression between normal bladder cell and bladder cancer cells were tested in western blot and PCR, and the underlying molecular mechanism was investigated.Results: RNA levels of C1QTNF6 were found to be differentially expressed in two independent public cohorts including TCGA database and GSE13507 from GEO database. The protein and RNA expressions C1QTNF6 in bladder cell lines were both significantly elevated than normal bladder cell line. High C1QTNF6 expressions were found in advanced T status, M status, pathological grade, AJCC stage compared with low C1QTNF6 expression group. The underlying mechanism may be explained by cell migration and invasion assays that bladder cancer cells 5637 and T24 were significantly reduced migration and invasion ability with the knock-down C1QTNF6 expressions. The low RNA expression group of C1QTNF6 demonstrated OS advantage over high-expression group in both TCGA and GSE13507 cohorts. Besides, protein expressions in tissues were further validated in HPA database and TMA. Survival analysis also indicated that the high expression of C1QTNF6 indicated unfavorable OS compared with low expressions group.Conclusions: High expression of C1QTNF6 predicted poor prognosis for bladder cancer patients, and the underlying mechanism is associated with cancer cell migration and invasion ability.

Sign in / Sign up

Export Citation Format

Share Document