scholarly journals Matrix metalloproteinase 7 (MMP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) downregulation complements PALG1 oncogene overexpression in pleomorphic adenoma pathogenesis

Genetika ◽  
2021 ◽  
Vol 53 (1) ◽  
pp. 339-348
Author(s):  
Boban Anicic ◽  
Nadja Nikolic ◽  
Jelena Carkic ◽  
Drago Jelovac ◽  
Zoran Jezdic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salivary Glands ◽  
Pleomorphic Adenoma ◽  
Benign Lesion ◽  
Tumor Biology ◽  
Mrna Levels ◽  
Quantitative Real Time Pcr ◽  
Matrix Metalloproteinase 7 ◽  
Mmp Genes ◽  
Gene Expression Levels

Pleomorphic adenoma (PA) is the most common neoplasm of salivary glands and consists of epithelial and mesenchymal components. Although a benign lesion, it harbors a potential for recurrence and malignant transformation. Also, due to its histological diversity and unpredictive behavior PA can represent both diagnostic and therapeutic challenge. Matrix metalloproteinases (MMPs) are well known modifiers of extracellular matrix (ECM) PA component and in conjunction with their endogenous tissue inhibitors (TIMPs) may influence PA tumor biology. PLAG1 oncogene also has an important role in PA; however, neither the exact mechanisms of its influence nor its interactions with other genes are completely elucidated. The aims of this study were to assess the expression of PLAG1, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 genes in PAs, and find a possible association of gene expression levels with clinical/epidemiological parameters of PA patients. Relative mRNA levels were assessed using Quantitative real-time PCR analyses in 15 PAs of the parotid gland and 5 normal salivary glands (NSGs). A statistically significant overexpression of PLAG1 was observed in PA compared to NSG samples (P=0.010); PA had 5.48 times higher mRNA levels than NSG. Out of the three analyzed MMP genes, significantly lower levels of MMP-7 were found in PA patients (P=0.026). TIMP2 was also downregulated in PA samples, compared to NSGs (P=0.040). MMP-7 and TIMP-2 mRNA levels were decreased 2.95 and 2.85 times respectively, in PA samples. No association was found between gene expression and clinical/epidemiological PA parameters. Our results suggest that PLAG1 overexpression with concomitant MMP7 and TIMP2 downregulation may contribute to PA development.

scholarly journals A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erik Bovinder Ylitalo ◽  
Elin Thysell ◽  
Mattias Landfors ◽  
Maria Brattsand ◽  
Emma Jernberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Bone Metastases ◽  
Metastatic Prostate Cancer ◽  
Tumor Biology ◽  
Receptor Activity ◽  
Mrna Levels ◽  
Androgen Receptor Activity ◽  
Patient Prognosis

Abstract Background Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity. Materials and methods Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity. Results Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT. Conclusions A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

scholarly journals Codon usage is an important determinant of gene expression levels largely through its effects on transcription

2016 ◽  
Vol 113 (41) ◽  
pp. E6117-E6125 ◽  
Author(s):  
Zhipeng Zhou ◽  
Yunkun Dang ◽  
Mian Zhou ◽  
Lin Li ◽  
Chien-hung Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Codon Usage ◽  
Important Determinant ◽  
Mrna Translation ◽  
Mrna Levels ◽  
Protein Coding ◽  
Expression Levels ◽  
Highly Expressed Genes ◽  
The Impact ◽  
Gene Expression Levels

Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.

Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mrna Expression ◽  
Advanced Colorectal Cancer ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mutational Status ◽  
Mrna Expression Levels ◽  
Gene Expression Levels

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.

scholarly journals Differential Expression of Virulence-Related Genes in Enterococcus faecalis in Response to Biological Cues in Serum and Urine

2002 ◽  
Vol 70 (8) ◽  
pp. 4344-4352 ◽  
Author(s):  
Brett D. Shepard ◽  
Michael S. Gilmore
Keyword(s):  
Gene Expression ◽  
Urinary Tract Infection ◽  
Enterococcus Faecalis ◽  
Mrna Levels ◽  
Quantitative Real Time Pcr ◽  
Limited Evidence ◽  
Control Of Gene Expression ◽  
Nosocomial Bacteremia ◽  
Serum And Urine

ABSTRACT Enterococci rank among leading causes of nosocomial bacteremia and urinary tract infection and are also a leading cause of community acquired subacute endocarditis. Limited evidence suggests that biological cues in serum and urine may play an important role in modulating enterococcal virulence at sites of infection. To determine the extent to which biological cues affect enterococcal virulence-associated gene expression, we used quantitative real-time PCR to compare mRNA levels in Enterococcus faecalis cultures grown in serum or urine to that achieved in laboratory medium. Both environment- and growth phase-specific variations were observed, demonstrating the occurrence of as-yet-uncharacterized mechanisms for control of gene expression in E. faecalis that may play an important role in vivo.

scholarly journals Dynamics Affect Nitrogen Retention, Ileal Amino Acid Digestibility, and Gene Expression Levels of Digestive Enzymes at Three Stages in Pigs Fed Two Levels of Low-Protein Diets

2019 ◽  
Author(s):  
Li Wu ◽  
Qinghua He ◽  
Wen Zhen ◽  
Tiejun Li ◽  
Peng Liao
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Treatment Group ◽  
Protein Intake ◽  
Digestive Enzymes ◽  
Growing Pigs ◽  
Mrna Levels ◽  
Expression Levels ◽  
Three Stages ◽  
Gene Expression Levels

This study was conducted to determine the dynamic effects of dietary crude protein (CP) intake on nitrogen (N) balance, ileal amino acid digestibility, and gene expression levels of digestive enzymes at three stages in pigs. In Experiment 1, 18 growing pigs (average body weight (BW) = 9.5 kg) were randomly assigned to one of three treatments (n = 6/treatment group), including normal (20% CP), low (17% CP), and very low (14% CP) protein intake. In Experiment 2, 18 growing pigs (average BW = 30 kg) were allotted randomly to one of three treatments (n = 6/treatment group), including normal (18% CP), low (15% CP), and very low (12% CP) protein intake. In Experiment 3, 18 growing pigs (average BW = 45 kg) were assigned randomly to one of three treatments (n = 6/treatment group), including normal (16% CP), low (13% CP), and very low (10% CP) protein intake. Growing pigs fed the 14% CP and 17% CP diets had lower final BW (P &lt; 0.05) and average daily gain (ADG) (P &lt; 0.05) compared to pigs fed the 20% CP diet. Reducing the dietary CP level from 20 to 14% decreased urinary N excretion by 52.8% (P &lt; 0.001) in Experiment 1. Reducing the dietary CP level from 18 to 12% decreased urinary N excretion by 55.3% (P &lt; 0.001) and reduced fecal N excretion by 34% (P &lt; 0.05) in Experiment 2. Reducing the dietary CP level from 16 to 10% decreased urinary N excretion by 56.4% (P &lt; 0.001) and fecal N excretion by 47.1% (P &lt; 0.001) in Experiment 3. Pigs fed the very low (14%, 12%, and 10% CP) diets showed higher digestibility for CP (P &lt; 0.05), His (P &lt; 0.05), Ile (P &lt; 0.05), Phe (P &lt; 0.05), Thr (P &lt; 0.05), Trp (P &lt; 0.05), Glu (P &lt; 0.05), and Ser (P &lt; 0.05) compared to pigs fed the normal (20%, 18%, and 16% CP) diets among the three experiments. Pigs fed the very low (14%, 12%, and 10% CP) diets showed higher mRNA levels for chymotrypsin C (P &lt; 0.01 in Experiment 1 and 2; P &lt; 0.05 in Experiment 3) compared to pigs fed the normal (20%, 18%, and 16% CP) diets among the three experiments. These results indicated that a reduction in dietary CP by 6% limited the growth performance of growing pigs, and a reduction of dietary CP by 3% supplemented with essential amino acids could reduce the excretion of N into the environment without affecting weight gain.

scholarly journals Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

2021 ◽  
Vol 22 (16) ◽  
pp. 8485
Author(s):  
Iranzu Gómez de Segura ◽  
Patricia Ahechu ◽  
Javier Gómez-Ambrosi ◽  
Amaia Rodríguez ◽  
Beatriz Ramírez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Mrna Levels ◽  
Expression Levels ◽  
The Impact ◽  
Ht 29 ◽  
Gene Expression Levels

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

Use of multidrug-resistance gene (MDR1) expression levels to predict outcome to adjuvant cisplatin/gemcitabine based chemotherapy in patients with with locally advanced urothelial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22081-e22081
Author(s):  
T. Gauler ◽  
A. C. Hoffman ◽  
P. Wild ◽  
C. Leicht ◽  
S. Bertz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Urothelial Cancer ◽  
Locally Advanced ◽  
Mdr1 Gene ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mdr1 Gene Expression ◽  
Mdr1 Expression ◽  
Advanced Urothelial Cancer ◽  
Gene Expression Levels

e22081 Background: The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp), whose function is the energy dependent export of substances from the inside of cells, and from membranes, to the outside. MDR1 mRNA levels have been shown to influence metabolism of cancer drugs. We tested whether MDR1 gene expression is associated with outcome in patients with locally advanced bladder cancer. Methods: 43 formalin fixed paraffin embedded (FFPE) tumor samples from patients with locally advanced and/or lymph node-positive bladder cancer undergoing treatment with cisplatin/gemcitabine were analyzed.FFPE tissues were dissected using laser-captured microdissection and analyzed for MDR1 expression using a quantitative real- time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: MDR1 was significantly correlated to overall survival. We included tumor stage (pT), lymph node status (pN) and the blood vessel invasion along with the measured gene expression in a stepwise multivariate Cox proportional hazards regression model. The overall model fit had a significance level of p=0.04 (<0.05). The relative risk for shorter survival in patients with High MDR1 expression was 1.9. Conclusions: These results suggest that MDR1 gene expression levels predict response and overall survival in patients with locally advanced urothelial cancer. MDR1 gene expression levels may allow the selection of patients who benefit likely from adjuvant cisplatin/gemcitabine based chemotherapy. Further studies are warranted to study this association. [Table: see text]

UL 16 Binding Protein 3 Gene Expression: Does It Have an Association With Alopecia Areata?

2020 ◽  
Author(s):  
Rania Azmy ◽  
Alaa Maraee ◽  
Eman Amer ◽  
Nermin Tayel ◽  
Wafaa Ahmed Shehata
Keyword(s):  
Gene Expression ◽  
Alopecia Areata ◽  
Disease Duration ◽  
Binding Protein ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Polymerase Chain ◽  
Insight Into ◽  
Gene Expression Levels ◽  
Gaining Insight

Abstract ObjectiveAlopecia Areata is one of the most widespread autoimmune diseases affecting both sexes of all ages and across all ethnic individuals. Genetics is considered to be a valuable tool for gaining insight into the disease’s pathogenesis. Association with UL 16 Binding Protein (ULBP) genes has been detected with autoimmune disorders.This study aimed to detect UL-16 Binding Protein -3 (ULBP3) gene expression levels in cases with AA and to correlate those levels with the clinical course of the disease.This study included 85 subjects: 55 patients with AA and 30 age- and sex-matched healthy controls. The expression level of ULBP3 mRNA was estimated using Real-Time Polymerase Chain Reaction (RT-PCR).Results Levels of ULBP3 mRNA in cases were significantly higher in patients with AA in comparison with controls. Also, there were significant correlations between ULBP3 mRNA levels and age of patients and disease duration in years. ULBP3 upregulation in AA enforces the theory that postulates the autoimmune nature of AA and ULBP3 may be involved in AA pathogenesis and its progression.

Molecular Effects of Rituximab on CLL Cells In Vivo: Rapid Increase in Serum Interferon gamma, Induction of a Distinct Tumor Cell Gene Expression Signature and Loss of CD20 Expression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2048-2048
Author(s):  
Adrian Wiestner ◽  
Elinor Lee ◽  
Berengere Vire ◽  
Federica Gibellini ◽  
Ndegwa Njuguna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Cells ◽  
Dominant Role ◽  
Tumor Biology ◽  
Gene Expression Signature ◽  
Leukemic Cells ◽  
Mrna Levels ◽  
Expression Signature ◽  
Protein Levels

Abstract Proposed mechanisms on how the monoclonal anti-CD20 antibody rituximab (R) depletes B-cells include antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In vitro studies have suggested that R induced pro-apoptotic signals contribute to clinical efficacy and may sensitize cells to chemotherapy. To investigate the effect of R on tumor biology in vivo, we analyzed the molecular changes in leukemic cells of 12 previously untreated CLL patients during the first R (375mg/m2) infusion. The median reduction of circulating tumor cells within 24h was 50% (range 0–67%). We first determined whether R affects gene expression in CLL cells obtained before and at 6h and 24h after the start of R. Cells were purified by CD19+ selection and gene expression was measured on Affymetrix HU133A 2.0 arrays. A one-way ANOVA test with a stringent cutoff (false discovery rate of &lt;20%) identified 69 genes whose expression increased &gt;50% at 6h compared to pre treatment, and 31 genes whose expression decreased by &gt;30%. Most of the up-regulated genes are known to be regulated by interferon (IFN) and include the pro-apoptotic genes IRF1, STAT1, FAS and OAS2. Of 12 cytokines assayed in the serum, we found that only IFNy, IL–6, IL–8, IL–10, and TNFa were induced by R with a peak at 2h. Consistent with a dominant role of IFNy on gene expression in the CLL cells, STAT1, a direct and essential mediator of IFNy signaling, was activated in circulating leukemic cells in vivo. In addition, when comparing the response between patients, IFNy serum protein levels correlated strongly with the intensity of the gene expression changes in the tumor cells (r=0.83, p=0.008). We could not detect any IFNy mRNA in CLL cells and conclude that the IFNy is most likely released by NK cells activated through FcyRIII signaling. Considering the long half-life of R, we were surprised to see that both cytokine serum levels and gene expression changes almost completely subsided by 24h. Intriguingly, among the few genes that were down-regulated by treatment, the gene encoding CD20 was the most strongly and consistently affected showing a 50% decrease in expression at 24h. We also assessed CD20 protein levels by Western blotting. Total CD20 levels were markedly decreased already at 6h and by 24h almost all CD20 had been lost. The more rapid and more pronounced decrease of CD20 protein as opposed to mRNA levels is consistent with a process previously described as shaving, during which R bound CD20 is pulled of the cell surface (Kennedy AD, J Immunol. 2004). Despite the absence of a clinical cytokine release syndrome, we observed basically identical changes in serum cytokines and gene expression with subsequent infusions in 2 patients analyzed. In summary, R induced a characteristic gene expression signature in CLL cells that is dominated by IFN response genes, many of which have well characterized pro-apoptotic functions. Thus, our data suggest that signaling for apoptosis is not so much a direct effect of R, but due to a complex immune response to the R coated CLL cells. Modified treatment schedules capable of delivering sustained pro-apoptotic signals hold promise for improved efficacy of R and should be explored.

Sign in / Sign up

Export Citation Format

Share Document