Project description:ObjectiveTo investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA.MethodsThe expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot.ResultsYY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated.ConclusionYY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.
Project description:BackgroundThe idea of Yin Yang Wu Xing, traditionally adopted and practiced in East-Asian medicine, has not been incorporated into the theoretical framework of modern medicine. It is therefore desired to show that Yin Yang Wu Xing is a manifestation of a higher-level faculty of cooperating system, thus making it suitable for a modern frame of thought.MethodsA higher-level faculty of the cooperating system is formulated in the scheme of Dual Five-Body Coordination. The stability of this scheme is examined mathematically and the feasibility of its physical realization is estimated.ResultsThe Dual Five-Body Coordination scheme, which overlaps substantially with the conceptual structure of Yin Yang Wu Xing, is stable and has survival merit. An imaginable conjecture based on physical reality confirms its physical feasibility.ConclusionThe Dual Five-Body Coordination scheme has potential utilization in various fields including biology and sociology. Once the theoretical framework is solidified, the Dual Five-Body Coordination scheme can be readily applied in practical research in modern medicine.
Project description:Yin Yang 1 (YY1) is a transcription factor with diverse and complex biological functions. YY1 either activates or represses gene transcription, depending on the stimuli received by the cells and its association with other cellular factors. Since its discovery, a biological role for YY1 in tumor development and progression has been suggested because of its regulatory activities toward multiple cancer-related proteins and signaling pathways and its overexpression in most cancers. In this review, we primarily focus on YY1 studies in cancer research, including the regulation of YY1 as a transcription factor, its activities independent of its DNA binding ability, the functions of its associated proteins, and mechanisms regulating YY1 expression and activities. We also discuss the correlation of YY1 expression with clinical outcomes of cancer patients and its target potential in cancer therapy. Although there is not a complete consensus about the role of YY1 in cancers based on its activities of regulating oncogene and tumor suppressor expression, most of the currently available evidence supports a proliferative or oncogenic role of YY1 in tumorigenesis.
Project description:Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain mature astrocytes in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.
Project description:Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regulators control expression of IL-17-dependent inflammatory genes, as well as the major target cells that respond to IL-17 signaling.
Project description:Yin Yang 1 (YY1) regulates both gene expression and protein modifications, and has shown a proliferative role in cancers. In this study, we demonstrate that YY1 promotes AKT phosphorylation at S473, a marker of AKT activation. YY1 expression positively correlated with AKT(S473) phosphorylation in a tissue microarray and cultured cells of breast cancer, but negatively associated with the distant metastasis-free survival of 166 breast cancer patients. YY1 promotes AKT phosphorylation at S473 through direct interaction with AKT, and the AKT-binding site is mapped to the residues G201-S226 on YY1. These residues are also involved in YY1 interaction with Mdm2, Ezh2, and E1A, and thus are designated as the oncogene protein binding (OPB) domain. YY1-promoted AKT phosphorylation relies on the OPB domain but is independent of either transcriptional activity of YY1 or the activity of phosphoinositide-3-kinases. We also determine that YY1-promoted mTORC2 access to AKT leads to its phosphorylation at S473. Importantly, a peptide based on the OPB domain blocks YY1 interaction with AKT and reduces AKT phosphorylation and cell proliferation. Thus, we demonstrate for the first time that YY1 promotes mTORC2-mediated AKT activation and disrupting YY1-AKT interaction by OPB domain-based peptide may represent a potential strategy for cancer therapy.
Project description:When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.
Project description:Persisters are a small fraction of quiescent bacterial cells that survive lethal antibiotics or stresses but can regrow under appropriate conditions. Persisters underlie persistent and latent infections and post-treatment relapse, posing significant challenges for the treatment of many bacterial infections. The current definition of persisters has drawbacks, and a Yin-Yang model is proposed to describe the heterogeneous nature of persisters that have to be defined in highly specific conditions. Despite their discovery more than 70 years ago, the mechanisms of persisters are poorly understood. Recent studies have identified a number of genes and pathways that shed light on the mechanisms of persister formation or survival. These include toxin-antitoxin modules, stringent response, DNA repair or protection, phosphate metabolism, alternative energy production, efflux, anti-oxidative defense and macromolecule degradation. More sensitive single-cell techniques are required for a better understanding of persister mechanisms. Studies of bacterial persisters have parallels in other microbes (fungi, parasites, viruses) and cancer stem cells in terms of mechanisms and treatment approaches. New drugs and vaccines targeting persisters are critical for improved treatment of persistent infections and perhaps cancers. Novel treatment strategies for persisters and persistent infections are discussed.
Project description:Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4(-)CD8(-) double-negative thymocytes, development to the CD4(+)CD8(+) double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53.
Project description:The mechanisms for regulation of the Inhibitor of Apoptosis (IAP) Survivin in cells undergoing stress associated with tumor development and the tumor microenvironment are not well understood. The stress response transcription factors HIF-1α and Yin Yang 1 (YY1) were hypothesized to contribute to the upregulation of Survivin in tumor cells. As expected, U2OS cells overexpressing HIF-1α showed a 2- to 3-fold transactivation when transfected. Surprisingly, when YY1 was overexpressed in this survivin promoter reporter system, luciferase expression was repressed 30- to 40-fold. YY1 involvement in survivin promoter repression was confirmed using siRNA directed against YY1. These studies showed that knockdown of YY1 releases the survivin promoter from the observed repression and leads to a 3- to 5-fold increase in promoter activity above basal levels. A U2OS cell line containing a stable YY1 Tet-off system was used to determine whether a temporal increase in YY1 expression affects Survivin protein levels. A low to moderate decrease in Survivin protein was observed 24h and 48h after Tet removal. Studies also confirmed that YY1 is capable of directly binding to the survivin promoter. Collectively, these findings identify novel basal transcriptional requirements of survivin gene expression which are likely to play important roles in the development of cancer and resistance to its treatment.