The effect of exposure to neighborhood violence on GR signaling in lung tumors [Spatial Transcriptomics]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1114097 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29113448.fastq.gz | Fastqsanger.gz | |||
| SRR29113449.fastq.gz | Fastqsanger.gz | |||
| SRR29113450.fastq.gz | Fastqsanger.gz | |||
| SRR29113451.fastq.gz | Fastqsanger.gz | |||
| SRR29113452.fastq.gz | Fastqsanger.gz |
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Project description:Despite lower rates and intensity of smoking, Black men experience a higher incidence of lung cancer compared to White men. The racial disparity in lung cancer is particularly pronounced in Chicago, a highly segregated urban city. Neighborhood conditions, particularly social stress, may play a role in lung tumorigenesis. Preliminary studies indicate that Black men residing in neighborhoods with higher rates of violent crime have significantly higher levels of hair cortisol, an indicator of stress response. To examine the relationship between social stress exposure and gene expression in lung tumors, we investigated glucocorticoid receptor (GR) binding in lung tumor samples in relation to GR target gene expression levels and zip code level residential neighborhood violence. Spatial transcriptomics and a version of ChIP-sequencing known as CUT & RUN were used. GR recruitment to chromatin was correlated with neighborhood violent crime rate and overall GR binding increased with increasing neighborhood violent crime rates. Among patients residing in high-violence neighborhoods, tumor samples, compared to normal neighboring lung tissue, had fewer GR binding sites. The opposite was seen in patients residing in low-violence neighborhoods, with tumor samples having more GR binding sites when compared to normal lung tissue. Tumor samples from patients living in high-violence neighborhoods exhibited increased GR recruitment to genes associated with greater tumor aggressiveness. Our findings suggest that exposure to neighborhood violence may influence tumor biology via reprogramming GR recruitment. Prioritizing lung cancer screening in neighborhoods with increased social stress, such as high violence, may reduce racial disparities in lung cancer.
2024-07-10 | GSE268049 | GEO
Project description:Despite lower rates and intensity of smoking, Black men experience a higher incidence of lung cancer compared to White men. The racial disparity in lung cancer is particularly pronounced in Chicago, a highly segregated urban city. Neighborhood conditions, particularly social stress, may play a role in lung tumorigenesis. Preliminary studies indicate that Black men residing in neighborhoods with higher rates of violent crime have significantly higher levels of hair cortisol, an indicator of stress response. To examine the relationship between social stress exposure and gene expression in lung tumors, we investigated glucocorticoid receptor (GR) binding in lung tumor samples in relation to GR target gene expression levels and zip code level residential neighborhood violence. Spatial transcriptomics and a version of ChIP-sequencing known as CUT & RUN were used. GR recruitment to chromatin was correlated with neighborhood violent crime rate and overall GR binding increased with increasing neighborhood violent crime rates. Among patients residing in high-violence neighborhoods, tumor samples, compared to normal neighboring lung tissue, had fewer GR binding sites. The opposite was seen in patients residing in low-violence neighborhoods, with tumor samples having more GR binding sites when compared to normal lung tissue. Tumor samples from patients living in high-violence neighborhoods exhibited increased GR recruitment to genes associated with greater tumor aggressiveness. Our findings suggest that exposure to neighborhood violence may influence tumor biology via reprogramming GR recruitment. Prioritizing lung cancer screening in neighborhoods with increased social stress, such as high violence, may reduce racial disparities in lung cancer.
2024-07-10 | GSE268048 | GEO
Project description:The effect of exposure to neighborhood violence on GR signaling in lung tumors [CUT&Run]
| PRJNA1114098 | ENA
Project description:Objectives Breastfeeding has short- and long-term health benefits for children and mothers, but US breastfeeding rates are suboptimal. Exposure to violence may contribute to these low rates, which vary by race/ethnicity. We studied: (1) whether patterns of violence exposure differ by race/ethnicity and (2) whether these patterns are associated with breastfeeding outcomes. Methods We conducted a secondary analysis of data drawn from self-report surveys completed by a convenience sample of low-income postpartum women (n?=?760) in upstate New York. Latent class analysis was used to identify groups of women with similar responses to seven violence measures, including childhood physical and/or sexual violence, experience of partner violence during or just after pregnancy (physical, emotional, verbal), and neighborhood violence (perceived or by ZIP code). Logistic regression and survival analysis were utilized to determine if classes were associated with breastfeeding initiation, duration, and exclusivity, controlling for demographics. Results Exposure to at least one form of violence was high in this sample (87%). We identified 4 classes defined by violence exposure (combining current and historical exposures). Violence exposure patterns differed between racial/ethnic groups, but patterns were inconsistently associated with breastfeeding plans or outcomes. For White women, history of violence exposure increased the likelihood of earlier breastfeeding cessation. By contrast, among Black women, history of violence exposure increased the likelihood of having a breastfeeding plan and initiating breastfeeding. Conclusions for Practice Some differences between violence exposure classes are likely due to the correlation between race/ethnicity and socioeconomic status in the community studied. Additional studies are warranted to better understand how exposure to violence is related to breastfeeding and how best to support women making decisions about intention, initiation, and duration of breastfeeding.
| S-EPMC5764770 | biostudies-other
Project description:The Glucocorticoid Receptor (GR) is both one of the most widely used clinical drug targets and a very potent metabolic regulator. GR belongs to the nuclear hormone receptor family of ligand-gated transcription factors that govern mammalian physiology. Upon ligand binding, GR enters the nucleus to regulate gene expression both positively and negatively. It is known to bind to consensus DNA sequences termed glucocorticoid response elements (GREs), but the mechanisms determining transcriptional activation versus repression remain an unresolved molecular paradox. Prevailing models suggest that tethering of GR to AP-1 or NF-κB via protein-protein interactions, rather than direct DNA binding, specifies negative regulation. However, here we show that the repression of inflammatory genes as well as all other glucocorticoid responses, require direct DNA binding of GR. Generating GR point mutant mice that retain the ability to tether via protein-protein interactions while unable to recognize DNA sequences, we demonstrate that response element recognition via the Zinc finger is absolutely required for both transcriptional activation and repression. We have used ChIP-Seq and RNA-Seq in inflammatory and metabolic cells and tissues together with proteomics to reveal that DNA binding of GR is necessary for the assembly of a functional SWI/SNF coregulator complex. Generally, the desired anti-inflammatory actions of GR are attributed to the silencing of inflammatory genes, while its adverse effects are believed to result from the transcriptional upregulation of metabolic targets. Our findings not only challenge classical models and dogmas of GR mediated gene regulation, but will provide an important basis for the development of novel immunosuppressants with reduced side effect profiles.
2020-07-07 | PXD013772 | Pride
Project description:BackgroundDating violence (DV) is a public health problem that could have serious repercussions for the health and well-being of a large number of adolescents. Several neighborhood characteristics could influence these behaviors, but knowledge on such influences is still limited. This study aims at (1) evaluating the associations between neighborhood characteristics and DV, and (2) assessing how spatial scale influences the estimations of the latter associations.MethodsThe Québec Health Survey of High School Students (2016-2017) was used to describe DV. Neighborhoods were operationalized with polygon-based network buffers of varying sizes (ranging from 250 to 1000 m). Multiple data sources were used to describe neighborhood characteristics: crime rate, alcohol outlet density (on-premises and off-premises), walkability, greenness, green spaces density, and youth organizations density. Gendered-stratified logistic regressions were used for assessing the association between neighborhood characteristics and DV.ResultsFor boys, off-premises alcohol outlet density (500 m) is associated with an increase in perpetrating psychological DV. Crime rate (500 m) is positively associated with physical or sexual DV perpetration, and crime rate (250 m) is positively associated with physical or sexual DV victimization. Greenness (1000 m) has a protective effect on psychological DV victimization. For girls, walkability (500 m to 1000 m) is associated with a decrease in perpetrating and experiencing psychological DV, and walkability (250 m) is negatively associated with physical or sexual DV victimization.ConclusionsSeveral neighborhood characteristics are likely to influence DV, and their effects depend on the form of DV, gender, and spatial scale. Public policies should develop neighborhood-level interventions by improving neighborhood living conditions.
| S-EPMC9210619 | biostudies-literature
Project description:Glucocorticoid (GC) response elements (GREs) are genomic segments that confer GC-regulated transcription by recruiting hormone-bound glucocorticoid receptor (GR) and nucleating assembly of transcriptional regulatory complexes (TRCs). The locations of GR binding, the functionality of those GR occupied regions (GORs) as GREs, and the molecular features and spatial organization that characterize active GREs are gene-, cell- and physiological-context specific, and poorly understood. Moreover, identification of the gene(s) targeted for regulation by a given GRE has been inferred by proximity, or examined outside the normal chromosomal context, rather than rigorously validated. We approached these issues in two human cell lines with distinct tissue origins, treated or not with a hormonal ligand that activates GR.
2020-12-18 | GSE163398 | GEO
Project description:Glucocorticoid receptor (GR) is a ligand dependent transcription factor that plays a central role in inflammation. Part of a complex cellular network, GR activity is further modulated via protein–protein interactions . The regulation of GR by 14-3-3 proteins has been previously reported, though with differing sites of phosphorylation identified and variable consequences assigned. Hence, we sought to examine this protein–protein interaction and, using phosphorylated GR peptides, biophysical studies and X-ray crystallography, we identified key residues within the ligand binding domain of GR, T524 and S617, whose phosphorylation results in recognition by 14-3-3. Investigation of the kinases responsible for phosphorylation of these sites assigned a key role for MINK1 and cell-based approaches confirmed the importance of these two GR phosphosites and MINK1 in GR–14-3-3 binding. Together our results provide a molecular-level insight into 14-3-3 regulation of GR and highlight both MINK1 and the GR–14-3-3 axis as potential targets for future therapeutic intervention.
2021-09-09 | PXD022364 | Pride
Project description:In this study, we analyze first whether there is a common spatial distribution of child maltreatment (CM) and intimate partner violence (IPV), and second, whether the risks of CM and IPV are influenced by the same neighborhood characteristics, and if these risks spatially overlap. To this end we used geocoded data of CM referrals (N = 588) and IPV incidents (N = 1450) in the city of Valencia (Spain). As neighborhood proxies, we used 552 census block groups. Neighborhood characteristics analyzed at the aggregated level (census block groups) were: Neighborhood concentrated disadvantage (neighborhood economic status, neighborhood education level, and policing activity), immigrant concentration, and residential instability. A Bayesian joint modeling approach was used to examine the spatial distribution of CM and IPV, and a Bayesian random-effects modeling approach was used to analyze the influence of neighborhood-level characteristics on small-area variations of CM and IPV risks. For CM, 98% of the total between-area variation in risk was captured by a shared spatial component, while for IPV the shared component was 77%. The risks of CM and IPV were higher in neighborhoods characterized by lower levels of economic status and education, and higher levels of policing activity, immigrant concentration, and residential instability. The correlation between the log relative risk of CM and IPV was .85. Most census block groups had either low or high risks in both outcomes (with only 10.5% of the areas with mismatched risks). These results show that certain neighborhood characteristics are associated with an increase in the risk of family violence, regardless of whether this violence is against children or against intimate partners. Identifying these high-risk areas can inform a more integrated community-level response to both types of family violence. Future research should consider a community-level approach to address both types of family violence, as opposed to individual-level intervention addressing each type of violence separately.
| S-EPMC5991672 | biostudies-literature