scholarly journals Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Joëlle Goulding ◽  
Sarah J. Mistry ◽  
Mark Soave ◽  
Jeanette Woolard ◽  
Stephen J. Briddon ◽  
...  
Keyword(s):  
Expression Levels ◽  
Ici 118,551 ◽  
Fluorescent Ligands ◽  
Subtype Selective ◽  
Low Expression

scholarly journals Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Steven F. Gameiro ◽  
Farhad Ghasemi ◽  
Peter Y. F. Zeng ◽  
Neil Mundi ◽  
Christopher J. Howlett ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Relative Level ◽  
Expression Levels ◽  
T Cell Infiltration ◽  
Molecular Features ◽  
Platinum Based Chemotherapy ◽  
Low Expression

Abstract Background Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear. Methods Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels. Results Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC. Conclusion These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC.

scholarly journals A link between expression level of long-non-coding RNA ZFAS1 in breast tissue of healthy women and obesity

2018 ◽  
Vol 33 (4) ◽  
pp. 500-506 ◽  
Author(s):  
Yaser Mansoori ◽  
Mohammad Bagher Tabei ◽  
Alireza Askari ◽  
Pantea Izadi ◽  
Abdolreza Daraei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Correlation ◽  
Breast Tissue ◽  
Breast Cancer Incidence ◽  
Reproductive History ◽  
Expression Level ◽  
Expression Levels ◽  
Healthy Women ◽  
Low Expression ◽  
High Bmi

Background: Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely ZFAS1 and SRA1 in cancer-free breast tissues of women. Methods: In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue samples. Results: It was found that women with body mass index (BMI)≥30 kg/m2 and BMI 25–29 kg/m2 show a low expression of ZFAS1 compared to the BMI<25 kg/m2 ( P=0.031 and P=0.027, respectively). Then, the correlation analysis disclosed a negative correlation of ZFAS1 low expression with increasing BMI (r=−0.194, P=0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the ZFAS1 and high BMI in women with menarche age below 14 (r=−221; P=0.028). Lastly, it was also revealed that there was a negative association of the low expression level of ZFAS1 with increasing BMI in women through regression models (B=−0.048, P=0.019). Conclusions: These findings suggest interesting clues about the links between high BMI and the expression levels of ZFAS1 in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.

miR-125b promotes cell proliferation by directly targeting Lin28 in glioblastoma stem cells with low expression levels of miR-125b

Neuroreport ◽  
2013 ◽  
pp. 1 ◽  
Author(s):  
Yi Wan ◽  
Guan Sun ◽  
Zhimin Wang ◽  
Jun Guo ◽  
Lei Shi
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Glioblastoma Stem Cells ◽  
Expression Levels ◽  
Low Expression

scholarly journals Purification of recombinant proteins from Escherichia coli at low expression levels by inverse transition cycling

2007 ◽  
Vol 360 (1) ◽  
pp. 166-168 ◽  
Author(s):  
Trine Christensen ◽  
Kimberly Trabbic-Carlson ◽  
Wenge Liu ◽  
Ashutosh Chilkoti
Keyword(s):  
Escherichia Coli ◽  
Recombinant Proteins ◽  
Expression Levels ◽  
Inverse Transition Cycling ◽  
Inverse Transition ◽  
Low Expression

Action of SDF-1/CXCR4 axis in liver metastasis of colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 530-530 ◽  
Author(s):  
Shinichiro Yamada ◽  
Mitsuo Shimada ◽  
Toru Utsunomiya ◽  
Satoru Imura ◽  
Yuji Morine ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Normal Liver ◽  
High Expression ◽  
Expression Level ◽  
Expression Levels ◽  
High Expression Group ◽  
Cxcr4 Axis ◽  
Low Expression ◽  
Liver Tissues

530 Background: It has recently been suggested that the SDF-1/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival in various cancer. In this study, we investigate the possible role of SDF-1/CXCR4 axis in colorectal liver metastasis. Methods: Both primary colorectal tumors and liver metastatic tumors were obtained from 12 patients with colorectal liver metastasis. Expression levels of CXCR4 and SDF-1 were determined using RT-PCR. In 4 patients with benign liver disease, the expression level of SDF-1 in normal liver tissues was also determined. We divided the 12 patients into two groups; high expression group (n=6) and low expression group (n=6) according to each expression level of SDF-1 and CXCR4, and compared the clinicopathological factors between the two groups. Results: 1. CXCR4 expression levels in primary tumor: The frequency of the peritoneal dissemination in the CXCR4 high expression group was higher than in the low expression group (p=0.07). Moreover, overall survival rate in the CXCR4 high expression group was significantly lower than that in the low expression group (3 year-survival rate: 67% vs. 100%, p<0.05). 2. CXCR4 in metastatic tumor tissues and SDF-1 in non-tumor liver tissues: The expression level of SDF-1 in non-tumor liver tissues was significantly higher than that in normal liver tissues (p<0.01). A significant correlation between the CXCR4 expression levels in metastatic tumor tissues and SDF-1 expression levels of non-tumor liver tissues (p<0.05). The number of metastatic liver tumors in the SDF-1 high expression group tended to be larger than that in the low expression group (p=0.12). Conclusions: The present data suggest that there is a significant association of the SDF-1/CXCR4 axis with enhanced liver metastasis and poor prognosis of the patients with colorectal liver metastasis. Furthermore, an enhanced expression of SDF-1 in non-tumor liver tissues may have an important role in the formation of liver metastasis.

scholarly journals Self inhibition of phagocytosis: The affinity of ‘marker of self’ CD47 for SIRPα dictates potency of inhibition but only at low expression levels

2010 ◽  
Vol 45 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Richard K. Tsai ◽  
Pia L. Rodriguez ◽  
Dennis E. Discher
Keyword(s):  
Expression Levels ◽  
Low Expression

Identification of Xenologs and Their Characteristic Low Expression Levels in the Cyanobacterium Synechococcus elongatus

2015 ◽  
Vol 80 (5-6) ◽  
pp. 292-304 ◽  
Author(s):  
Gilberto Álvarez-Canales ◽  
Guadalupe Arellano-Álvarez ◽  
Carmen M. González-Domenech ◽  
Fernando de la Cruz ◽  
Andrés Moya ◽  
...  
Keyword(s):  
Synechococcus Elongatus ◽  
Expression Levels ◽  
Low Expression

scholarly journals Epigenetic Allelic States of a Maize Transcriptional Regulatory Locus Exhibit Overdominant Gene Action

Genetics ◽  
1998 ◽  
Vol 150 (2) ◽  
pp. 891-897 ◽  
Author(s):  
Jay B Hollick ◽  
Vicki L Chandler
Keyword(s):  
Gene Action ◽  
High Expression ◽  
Regulatory Mechanisms ◽  
Epigenetic Changes ◽  
Anthocyanin Pigment ◽  
Pigment Synthesis ◽  
Expression Levels ◽  
Sexually Transmitted ◽  
Transcriptional Regulatory ◽  
Low Expression

Abstract Using alleles of the maize purple plant locus (pl), which encodes a transcriptional regulator of anthocyanin pigment synthesis, we describe a case of single-locus heterosis, or overdominance, where the heterozygote displays a phenotype that is greater than either homozygote. The Pl-Rhoades (Pl-Rh) allele is subject to epigenetic changes in gene expression, resulting in quantitatively distinct expression states. Allelic states with low-expression levels, designated Pl′-mahogany (Pl′-mah), are dominant to the high-expression state of Pl-Rh. Pl′-mah states retain low-expression levels in subsequent generations when homozygous or heterozygous with Pl-Rh. However, Pl′-mah alleles frequently exhibit higher expression levels when heterozygous with other pl alleles; illustrating an overdominant allelic relationship. Higher expression levels are also observed when Pl′-mah is hemizygous. These results suggest that persistent allelic interactions between Pl′-mah and Pl-Rh are required to maintain the low-expression state and that other pl alleles are missing sequences required for this interaction. The Pl-Rh state can be sexually transmitted from Pl′-mah/pl heterozygotes, but not from Pl′-mah hemizygotes, suggesting that fixation of the high-expression state may involve synapsis. The existence of such allele-dependent regulatory mechanisms implicates a novel importance of allele polymorphisms in the genesis and maintenance of genetic variation.

scholarly journals R-2HG/KDM2B/RIPK1 Signaling Mediates Necroptosis in Myelodysplastic Syndromes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5049-5049
Author(s):  
Shuanghong Zhu ◽  
Chen Mei ◽  
Hongyan Tong ◽  
Jie Jin
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Cell Membrane ◽  
Membrane Permeability ◽  
Cell Lines ◽  
Myelodysplastic Syndromes ◽  
Poor Prognosis ◽  
Cell Membrane Permeability ◽  
Expression Levels ◽  
Low Expression

Introduction: Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders and manifested as ineffective hematopoiesis, refractory cytopenia and a propensity to evolve into acute myeloid leukemia (AML). Isocitrate dehydrogenase 1/2 (IDH1/2) mutations are common in both MDS and AML. Mutated IDH produces R-2-hydroxyglutarate (R-2HG) which inhibits multiple α-ketoglutarate/α-KG-dependent dioxygenases by competing against α-KG binding. Recent studies have demonstrated that R-2-HG can abrogates leukemic growth and induce leukemia cell death. Several nonapoptotic cell death have been identified, including phosphoribosyl pyrophosphate (PPRP)-1 mediated necrosis, pyroptosis, ferroptosis and necroptosis. By now, the specific type of cell death by which R-2-HG exerts anti-tumor effects is still unknown. Results: (1) (2R)-Octyl-2-HG exhibited anti-tumor effect on SKM-1, THP-1, Molm-13, HL-60 cell lines and bone marrow mononuclear cells from MDS and AML patients in a dose- and time-dependent manner. The overexpression of IDH2 mutation induced by doxycycline significantly decreased the viability of AML cell lines, and the inhibition rate was related to the dose of doxycycline. (2R)-Octyl-2-HG promotes apoptosis and causes G0/G1 phase arrest. (2) R-2-HG leads to increased expression of RIPK1 in high-risk MDS cells. The results of gene enrichment analysis indicated that the apoptotic pathway was enriched in (2R)-Octyl-2-HG groups, and the expression of RIPK1 gene was increased in all three (SKM-1, NOMO-1 and MA9.3ITD) (2R)-Octyl-2-HG groups. After treatment with (2R)-Octyl-2-HG, the mRNA and protein expression levels of RIPK1 gene were increased. (3) R-2-HG triggers RIPK1-dependent necroptosis and occurs earlier than apoptosis. Within 10 hours after treatment with (2R)-Octyl-2-HG, cell membrane permeability was disrupted, interactions between RIPK1 and caspase 8 increased, as well as phosphorylated MLKL level. However, caspase activity did not increase significantly, suggesting that necroptosis occurs earlier than apoptosis. With RIPK1 inhibitor Necrostatin-1 and (2R)-Octyl-2-HG co-treating cells, proliferation inhibition was reduced, cell membrane permeability was more stable and RIPK1-caspase8 complex was difficult to form. The same phenomenon occurs in SKM-1 cells stably transfected with RIPK1 shRNA virus, suggesting that RIPK1-dependent necroptosis is involved in cell death caused by (2R)-Octyl-2-HG. (4) In vivo experiments demonstrated that necroptosis by R-2-HG is dependent on the expression of RIPK. In RIPK1 shRNA MDS mice, the tumor burden showed a decreasing trend, but did not show a significant change in the R-2-HG treatment group. Treatment of scramble shRNA MDS mice with R-2-HG resulted in significantly smaller tumors in the spleen and less engrafment of CD45+ cells in bone marrow. (5) Low RIPK1 expression predicts poor prognosis in MDS patients. Data from the TCGA and GEO public databases indicate that RIPK1 expression is reduced in MDS and AML patients compared to healthy controls. Survival analysis showed that patients with lower RIPK1 expression levels had significantly shorter overall survival (OS) than patients with higher RIPK1 expression levels. MDS patients with lower RIPK1 expression levels progress to leukemia more frequently. (6) Inhibition of KDM2B induces necroptosis independently. Western blot assay shows the knockdown of KDM2B, upregulation of RIPK1 and increased levels of p-MLKL. Analysis of cell numbers showed that proliferation ceased from 4 days after doxycycline treatment onwards in shKDM2B cells. Co-IP assay shows the formation of RIPK1-caspase8 complex. Conclusion: This study confirmed that R-2-HG inhibited the viability of MDS and AML cells. R-2-HG increased the expression of RIPK1 in MDS cells, inducing necroptosis. Necroptosis occurred earlier than apoptosis. Inhibition of RIPK1 can alleviate the inhibitory effect of R-2-HG on MDS and AML cells. Clinical studies have shown that low expression of the RIPK1 gene is associated with poor prognosis in patients with MDS and AML. MDS patients with low expression of RIPK1 was more likely to progress to leukemia. Inhibition of KDM2B can induce necroptosis independently. Disclosures No relevant conflicts of interest to declare.

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