scholarly journals Alteration to the SWI/SNF complex in human cancers

2011 ◽  
Vol 4 (2) ◽  
pp. 89
Author(s):  
Vanessa S. Gordon ◽  
Colin Rogers ◽  
David Reisman
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cell Adhesion ◽  
Growth Control ◽  
Cellular Growth ◽  
Cancer Development ◽  
Catalytic Subunits ◽  
Cancer Types ◽  
Potential Impact ◽  
The Impact

The SWI/SNF complex is a key catalyst for gene expression and regulates a variety of pathways, many of which have anticancer roles. Its central roles in cellular growth control, DNA repair, differentiation, cell adhesion and development are often targeted, and inactivated, during cancer development and progression. In this review, we will discuss what is known about how SWI/SNF is inactivated, and describe the potential impact of abrogating this complex. BRG1 and BRM are the catalytic subunits which are essential for SWI/SNF function, and thus, it is not surprising that they are lost in a variety of cancer types. As neither gene is mutated when lost, the mechanism of suppression, as well as the impact of potential gene activity restoration, are reviewed.

scholarly journals Mutation Enrichment and Transcriptomic Activation Signatures of 419 Molecular Pathways in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 271 ◽  
Author(s):  
Marianna A. Zolotovskaia ◽  
Victor S. Tkachev ◽  
Alexander P. Seryakov ◽  
Denis V. Kuzmin ◽  
Dmitry E. Kamashev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Gene Networks ◽  
The Other ◽  
Molecular Pathways ◽  
Dna Mutations ◽  
Whole Exome ◽  
Pathway Activation ◽  
Cancer Types ◽  
First Time

Carcinogenesis is linked with massive changes in regulation of gene networks. We used high throughput mutation and gene expression data to interrogate involvement of 278 signaling, 72 metabolic, 48 DNA repair and 47 cytoskeleton molecular pathways in cancer. Totally, we analyzed 4910 primary tumor samples with individual cancer RNA sequencing and whole exome sequencing profiles including ~1.3 million DNA mutations and representing thirteen cancer types. Gene expression in cancers was compared with the corresponding 655 normal tissue profiles. For the first time, we calculated mutation enrichment values and activation levels for these pathways. We found that pathway activation profiles were largely congruent among the different cancer types. However, we observed no correlation between mutation enrichment and expression changes both at the gene and at the pathway levels. Overall, positive median cancer-specific activation levels were seen in the DNA repair, versus similar slightly negative values in the other types of pathways. The DNA repair pathways also demonstrated the highest values of mutation enrichment. However, the signaling and cytoskeleton pathways had the biggest proportions of representatives among the outstandingly frequently mutated genes thus suggesting their initiator roles in carcinogenesis and the auxiliary/supporting roles for the other groups of molecular pathways.

scholarly journals Integrative Pan-Cancer Analysis Reveals Decreased Melatonergic Gene Expression in Carcinogenesis and RORA as a Prognostic Marker for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zou ◽  
Huaqin Sun ◽  
Yating Guo ◽  
Yidan Shi ◽  
Zhiyu Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Prognostic Marker ◽  
Nuclear Receptor ◽  
Expression Patterns ◽  
Cancer Development ◽  
Metabolic Genes ◽  
Intracellular Receptor ◽  
Cancer Types ◽  
The Relationship

BackgroundMelatonin has been shown to play a protective role in the development and progression of cancer. However, the relationship between alterations in the melatonergic microenvironment and cancer development has remained unclear.MethodsWe performed a comprehensive investigation on 12 melatonergic genes and their relevance to cancer occurrence, progression and survival by integrating multi-omics data from microarray analysis and RNA sequencing across 11 cancer types. Specifically, the 12 melatonergic genes that we investigated, which reflect the melatonergic microenvironment, included three membrane receptor genes, three nuclear receptor genes, two intracellular receptor genes, one synthetic gene, and three metabolic genes.ResultsWidely coherent underexpression of nuclear receptor genes, intracellular receptor genes, and metabolic genes was observed in cancerous samples from multiple cancer types compared to that in normal samples. Furthermore, genomic and/or epigenetic alterations partially contributed to these abnormal expression patterns in cancerous samples. Moreover, the majority of melatonergic genes had significant prognostic effects in predicting overall survival. Nevertheless, few corresponding alterations in expression were observed during cancer progression, and alterations in expression patterns varied greatly across cancer types. However, the association of melatonergic genes with one specific cancer type, hepatocellular carcinoma, identified RORA as a tumor suppressor and a prognostic marker for patients with hepatocellular carcinoma.ConclusionsOverall, our study revealed decreased melatonergic gene expression in various cancers, which may help to better elucidate the relationship between melatonin and cancer development. Taken together, our findings highlight the potential prognostic significance of melatonergic genes in various cancers.

scholarly journals The Impact of Bioactive Surfaces in the Early Stages of Osseointegration: An In Vitro Comparative Study Evaluating the HAnano® and SLActive® Super Hydrophilic Surfaces

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Rodrigo A. da Silva ◽  
Geórgia da Silva Feltran ◽  
Marcel Rodrigues Ferreira ◽  
Patrícia Fretes Wood ◽  
Fabio Bezerra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Cell Cycle Progression ◽  
Cellular Adhesion ◽  
Biological Behavior ◽  
Early Stages ◽  
Genes Encoding ◽  
Bioactive Surfaces ◽  
The Impact

There is an increased effort on developing novel and active surfaces in order to accelerate their osteointegration, such as nanosized crystalline hydroxyapatite coating (HAnano®). To better understand the biological behavior of osteoblasts grown on HAnano® surface, the set of data was compared with SLActive®, a hydrophilic sandblasted titanium surface. Methodologically, osteoblasts were seeded on both surfaces up to 72 hours, to allow evaluating cell adhesion, viability, and set of genes encoding proteins related with adhesion, proliferation, and differentiation. Our data shows HAnano® displays an interesting substrate to support cell adhesion with typical spread morphologic cells, while SLActive®-adhering cells presented fusiform morphology. Our data shows that the cellular adhesion mechanism was accompanied with upexpression of integrin β1, Fak, and Src, favoring the assembling of focal adhesion platforms and coupling cell cycle progression (upmodulating of Cdk2, Cdk4, and Cdk6 genes) in response to HAnano®. Additionally, both bioactive surfaces promoted osteoblast differentiation stimulus, by activating Runx2, Osterix, and Alp genes. Although both surfaces promoted Rankl gene expression, Opg gene expression was higher in SLActive® and this difference reflected on the Rankl/Opg ratio. Finally, Caspase1 gene was significantly upmodulated in response to HAnano® and it suggests an involvement of the inflammasome complex. Collectively, this study provides enough evidences to support that the nanohydroxyapatite-coated surface provides the necessary microenvironment to drive osteoblast performance on dental implants and these stages of osteogenesis are expected during the early stages of osseointegration.

scholarly journals Integrated Analysis Reveals hsa-miR-142 as a Representative of a Lymphocyte-Specific Gene Expression and Methylation Signature

2012 ◽  
Vol 11 ◽  
pp. CIN.S9037 ◽  
Author(s):  
Bill Andreopoulos ◽  
Dimitris Anastassiou
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Specific Gene ◽  
Data Types ◽  
Multiple Cancer ◽  
Specific Expression ◽  
Cancer Types ◽  
Cell Cell

Gene expression profiling has provided insights into different cancer types and revealed tissue-specific expression signatures. Alterations in microRNA expression contribute to the pathogenesis of many types of human diseases. Few studies have integrated all levels of gene expression, miRNA and methylation to uncover correlations between these data types. We performed an integrated profiling to discover instances of miRNAs associated with a gene expression and DNA methylation signature across multiple cancer types. Using data from The Cancer Genome Atlas (TCGA), we revealed a concordant gene expression and methylation signature associated with the microRNA hsa-miR-142 across the same samples. In all cancer types examined, we found a signature of co-expression of a gene set R and methylated sites M, which correlate positively (M+) or negatively (M–) with the expression of hsa-miR-142. The set R consistently contains many genes, such as TRAF3IP3, NCKAP1L, CD53, LAPTM5, PTPRC, EVI2B, DOCK2, LCP2, CYBB and FYB. The signature is preserved across glioblastoma, ovarian, breast, colon, kidney, lung, uterine and rectum cancer. There is 28% overlap of methylation sites in M between glioblastoma (GBM) and ovarian cancer. There is 60% overlap of genes in R between GBM and ovarian ( P = 1.3e−-11). Most of the genes in R are known to be expressed in lymphocytes and haematopoietic stem cells, while M reflects membrane proteins involved in cell-cell adhesion functions. We speculate that the hsa-miR-142 associated signature may signal haematopoietic-specific processes and an accumulation of methylation events triggering a progressive loss of cell-cell adhesion. We also observed that GBM samples belonging to the proneural subtype tend to have underexpressed hsa-miR-142 and R genes, hypomethylated M+ and hypermethylated M–, while the mesenchymal samples have the opposite profile.

scholarly journals Evidence for Quantum Chemical Effects in Receptor-Ligand Binding Between Integrin and Collagen Fragments — A Computational Investigation With an Impact on Tissue Repair, Neurooncolgy and Glycobiology

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Eckert ◽  
Jan von Cosel ◽  
Benedict Kamps ◽  
Hans-Christian Siebert ◽  
Ruiyan Zhang ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Adhesion ◽  
Metal Ions ◽  
Quantum Chemical ◽  
Tissue Repair ◽  
Biological Functions ◽  
Tumor Tissues ◽  
Staining Methods ◽  
Potential Impact ◽  
The Impact

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin – NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin–carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co2+ ions seem to bind stronger to integrin than Mg2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological–glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.

scholarly journals The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1634 ◽  
Author(s):  
Ng Desi ◽  
Yvonne Tay
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Rna Processing ◽  
Cancer Development ◽  
Butterfly Effect ◽  
And Function ◽  
Post Transcriptional Regulation ◽  
The Impact ◽  
Rna Transcript

Post-transcriptional regulation plays a key role in modulating gene expression, and the perturbation of transcriptomic equilibrium has been shown to drive the development of multiple diseases including cancer. Recent studies have revealed the existence of multiple post-transcriptional processes that coordinatively regulate the expression and function of each RNA transcript. In this review, we summarize the latest research describing various mechanisms by which small alterations in RNA processing or function can potentially reshape the transcriptomic landscape, and the impact that this may have on cancer development.

Regulation of nutrient partitioning growth and lactation

1993 ◽  
Vol 44 (3) ◽  
pp. 523 ◽  
Author(s):  
R Bickerstaffe
Keyword(s):  
Gene Expression ◽  
Growth Hormones ◽  
Cellular Growth ◽  
Intrinsic Signals ◽  
Metabolic Genes ◽  
Secondary Messengers ◽  
Nutrient Partitioning ◽  
The Impact ◽  
Tissue Receptors

This paper will emphasize the impact of growth and lactation on partitioning nutrients, the role of biological signals and whether such signals can be influenced or modified. Factors considered are the mechanisms of controlling cell cycling, growth and differentiation; interaction or cross-talking between tissues (autocrinepeptides, tissue receptors, secondary messengers); effect of extrinsic and intrinsic signals on cellular growth (growth hormones, oncogenes); and manipulation of nutrient partitioning (mutated receptors, gene expression, targeting metabolic genes).

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