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：
10203786
负责人：
DEEPAK KUMAR
金额：
$ 60.74万
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 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203786
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.

项目概要/摘要标题：前列腺癌社会因素的分子决定因素前列腺癌不成比例地影响非裔美国 (AA) 男性，其发病率和死亡率较高社会经济地位（SES）和社会压力（例如邻里因素）广泛存在。被认为是这种健康差异的首要驱动因素，但它们与生物的关联和转化下丘脑-垂体-肾上腺轴（HPA）的应激和发病机制尚不清楚。调节压力反应，并被认为可以介导对细胞诱导的社会压力影响 HPA 轴调节控制糖皮质激素的皮质醇水平。 (GC) 社交压力后的反应除了皮质醇外，瘦素水平也被证明为这些应激激素可以调节影响发病机制的细胞信号传导。 MicroRNA 是高度稳定的非编码小 21-23nt 基因的表观遗传元件。调节性 RNA 主要通过靶向 3'UTR 起作用；它们在癌细胞存活中的作用已被研究，我们最近研究了前列腺癌的增殖、转移以及耐药性和侵袭性 PCa 的生物标志物。鉴定出 PCa 组织和体液（血清和尿液）中种族不同的差异表达 miRNA 糖皮质激素和瘦素信号传导均已被证明影响的表达。在这项提案中，我们将测试人类和实验室模型中的 miRNA。邻里因素转化为持续的生物压力，扰乱应激激素的水平，例如皮质醇和瘦素会导致表观遗传机制的改变，包括 miRNA 的表达。该提案将分析非裔美国人 (AA) 前列腺癌中的循环 microRNA 和应激激素水平接下来，我们将介绍华盛顿特区都会区社会地位和社会压力不同的患者。研究应激激素和选定的 microRNA 在调节癌症特征方面的相互作用。我们将通过识别 miRNA 靶点和相关途径来研究 miRNA 靶点应激标记本研究将从机制上表征社会压力期间调节途径的选定 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受社会压力调节并导致健康差异。了解社会的这些生物学影响。压力将显着影响非洲侵袭性 PCa 的诊断、预后和治疗开发美国人。