Molecular Determinants of Social Factors in Prostate Cancer

前列腺癌社会因素的分子决定因素

• 批准号: 10408227
• 负责人: DEEPAK KUMAR
• 金额: $ 11.21万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-26 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408227
• 关键词: 3' 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

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 和侵袭性疾病。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 应激及其发病机制尚不清楚。下丘脑-垂体-肾上腺轴 (HPA) 调节应激反应，并被认为可以介导社会应激对细胞的影响 癌症结果的生理学种族差异。 HPA 轴调节皮质醇水平，从而控制糖皮质激素 (GC) 社交压力后的反应。除了皮质醇之外，瘦素水平也被证明为 应激反应的效应器。这种应激激素可以调节影响发病机制的取消细胞信号传导 和结果。 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 发挥作用；人们已经研究了它们在癌细胞存活中的作用， 增殖、转移以及耐药性和侵袭性 PCa 的生物标志物。我们最近有 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 潜在的生物标志物。糖皮质激素和瘦素信号传导均已被证明会影响 人类和实验室模型中的 miRNA。在本提案中，我们将测试以下假设：社会和 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。这 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 华盛顿特区都会区的患者具有不同的社会经济地位和社会压力。接下来，我们将 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。最后， 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 机械地表征社会压力期间调节途径的选定 miRNA。这项研究将 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。

项目成果

Serotonin induced hepatic steatosis is associated with modulation of autophagy and notch signaling pathway.

• DOI: 10.1186/s12964-018-0282-6
• 发表时间: 2018-11-08
• 期刊: Cell communication and signaling : CCS
• 作者: Niture S;Gyamfi MA;Kedir H;Arthur E;Ressom H;Deep G;Kumar D
• 通讯作者: Kumar D

Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases.

• DOI: 10.1155/2021/9564297
• 发表时间: 2021
• 期刊: Journal of toxicology
• 影响因子: 2.9
• 作者: Niture S;Lin M;Qi Q;Moore JT;Levine KE;Fernando RA;Kumar D
• 通讯作者: Kumar D

COVID-19 vaccine hesitancy in underserved communities of North Carolina.

• DOI: 10.1371/journal.pone.0248542
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Doherty IA;Pilkington W;Brown L;Billings V;Hoffler U;Paulin L;Kimbro KS;Baker B;Zhang T;Locklear T;Robinson S;Kumar D
• 通讯作者: Kumar D

Management of Isolated Local Failures Following Stereotactic Body Radiation Therapy for Low to Intermediate Risk Prostate Cancer.

• DOI: 10.3389/fonc.2020.551491
• 发表时间: 2020
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Aghdam N;Pepin AN;Creswell M;Hsieh K;Smith C;Drescher N;Danner M;Ayoob M;Yung T;Lei S;Kumar D;Collins BT;Lischalk JW;Krishnan P;Suy S;Lynch J;Bandi G;Hankins RA;Collins SP
• 通讯作者: Collins SP

KCNQ1OT1: An Oncogenic Long Noncoding RNA.

• DOI: 10.3390/biom11111602
• 发表时间: 2021-10-29
• 期刊: Biomolecules
• 影响因子: 5.5
• 作者: Cagle P;Qi Q;Niture S;Kumar D
• 通讯作者: Kumar D