Molecular Determinants of Social Factors in Prostate Cancer

前列腺癌社会因素的分子决定因素

基本信息

批准号：
10369300
负责人：
DEEPAK KUMAR
金额：
$ 5.17万
依托单位：
NORTH CAROLINA CENTRAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-26 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369300
关键词：
3&apos Untranslated Regions Academic Medical Centers Affect African American Age Apoptosis Area Back Biological Biological Markers Body Fluids Body mass index Cancer Control Cancer Patient Caucasians Cell Survival Cell physiology Cessation of life Clinical Complex Consequentialism Country Data Death Rate Depressed mood Diagnosis Disease District of Columbia Drug resistance Elements Environment Epigenetic Process Exhibits Fibrinogen Glucocorticoids Hormones Human Hydrocortisone Incidence Indolent Laboratories Leptin Link Malignant Neoplasms Malignant neoplasm of prostate Measures Mediating MicroRNAs Modeling Molecular Neighborhoods Neoplasm Metastasis Outcome Pathogenesis Pathway interactions Patients Physiological Prognosis Quality of life RNA Radiation therapy Regulation Regulator Genes Resistance Role Sampling Serum Signal Transduction Social Environment Social isolation Socioeconomic Status Stress Testing Tissues Translating Translations Untranslated RNA Urine Violence base biological adaptation to stress cancer cell cancer health disparity castration resistant prostate cancer circulating microRNA cytokine differential expression driving force epigenome ethnic diversity experience health disparity hypothalamic-pituitary-adrenal axis inhibitor/antagonist loss of function men miRNA expression profiling mortality potential biomarker prostate cancer cell prostate cancer metastasis prostate carcinogenesis racial disparity response segregation social social determinants social factors social implication social stress socioeconomics stressor therapy development transcriptome volunteer

项目摘要

Project Summary/Abstract Title: Molecular Determinants of Social Factors in Prostate Cancer Prostate cancer disproportionately affects African American (AA) men with higher incidence, mortality and aggressive disease. Socioeconomic status (SES) and social stress such as neighborhood factors are widely regarded as the foremost driver of such health disparities however their association and translation to biological stress and mechanisms on pathogenesis are poorly understood. Hypothalamic-pituitary-adrenal axis (HPA) modulates stress response and has been suggested to mediate social stress induced effects on cellular physiology racial disparities in cancer outcomes. HPA-axis modulates cortisol levels controlling the glucocorticoid (GC) response following a social stress. In addition to cortisol, Leptin levels have been also demonstrated as effectors of stress response. Such stress hormones can modulate cancel cell signaling affecting pathogenesis and outcomes. MicroRNAs are epigenetic elements that are highly stable noncoding small 21-23nt gene- regulatory RNAs acting primarily by targeting 3’UTRs; their roles have been studied in cancer cell survival, proliferation, and metastasis as well as biomarkers of resistance and aggressive PCa. We have recently identified racially distinct differentially expressed miRNAs in PCa tissues and body fluids (serum and urine) as potential biomarker. Both Glucocorticoid and leptin signaling have been shown to affect the expression of miRNAs in human and laboratory models. In this proposal, we will test the hypothesize that social and neighborhood factors translate into continuous biological stress perturbing the levels of stress hormones such as cortisol and leptin resulting in alteration of epigenetic machinery including expression of miRNAs. The proposal will analyze circulating microRNAs and stress hormone levels in African American (AA) prostate cancer patients of the Washington DC metro area with differential socioeconomic status and social stress. Next, we will study the interplay between stress hormones and selected microRNAs in modulating cancer hallmarks. Finally, we will study miRNA-targets-stress markers by identifying miRNA targets and pathways involved to mechanistically characterize selected miRNAs for pathways modulated during social stress. This study will bridge the gap between social factors and biological determinants by studying logical epigenetic mechanisms modulated by social stress and causing health disparities. Understanding these biological implications of social stress will significantly impact diagnosis, prognosis and treatment development for aggressive PCa in African Americans.

项目摘要/摘要标题：前列腺癌社会因素的分子决定因素前列腺癌疏远影响影响影响影响影响影响影响的影响的影响美国（AA）男性发病率更高，死亡率和侵略性疾病。被认为是这种健康健康的最重要的驱动力，但是它们的关联和转化为生物学人们对发病机理的压力和机制被理解。调节应力应力应力应力菌丝系串以介导社会压力引起对细胞的影响癌症的生理种族差异。（GC）在社会压力下的反应。应力反应的应力效应因素。和结果。主要通过靶向3'UTR的调节性RNA在癌细胞存活中研究我们最近有扩散，转移以及抗性和侵略性PCA的生物标志物在PCA组织和体液（血清和尿液）中鉴定出种族不同的差异表达的miRNA为潜在的生物标志物。人类和实验室模型中的miRNA。邻里因素转化为连续的生物压力，使压力激素的水平扰动这样由于皮质醇和瘦素导致表观遗传性的机械性改变，包括miRNA的表达提出分析的非洲裔美国人（AA）前列腺癌中循环的microRNA和应力激素水平华盛顿特区地铁Atro的患者接下来是社会经济地位和社会压力最终，研究应力激素和选定的microRNA之间的相互作用。我们将通过确定涉及的miRNA目标和途径到机械学表征了在社会压力期间调节的途径的选定miRNA 通过研究逻辑表观遗传机制来弥合社会因素和生物决定因素之间的差距由社会压力调节并导致健康。压力将显着影响非洲侵略性PCA的诊断，预后和信任发展美国人。