MICRORNAS in AFRICAN AMERICAN PROSTATE CANCER

非裔美国人前列腺癌中的微小RNA

基本信息

批准号：
8323295
负责人：
DEEPAK KUMAR
金额：
$ 16.01万
依托单位：
UNIVERSITY OF THE DISTRICT OF COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8323295
关键词：
Affect Affinity African American American Cancer Society Apoptosis Basic Science Benign Binding Biological Biological Markers Biological Process Biology Body Fluids Cancer Biology Cancer Etiology Cancer Patient Case-Control Studies Caucasians Caucasoid Race Cell Proliferation Cells Cessation of life Code Communities Data Death Rate Development Disease Disease Progression Early Diagnosis Ethnic group Functional RNA Future Gene Expression Gene Expression Regulation Gene Structure Genes Grant Health Incidence Investigation LNCaP Length Link Longitudinal Studies Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Messenger RNA MicroRNAs Molecular Molecular Target Mutation Neoplasm Metastasis Nucleotides Oncogenes Oncogenic Outcome Pathway interactions Patients Pattern Phenotype Pilot Projects Population Predisposition Prevention Prostate Proteins Public Health Publishing RNA Regulation Regulator Genes Reporting Research Resistance development Risk Risk Factors Role Sampling Serum Small RNA Socioeconomic Factors Structure of base of prostate Testing Tissues Tumor Biology Tumor Suppressor Genes angiogenesis base cancer health disparity cancer initiation cancer risk cancer therapy gene function health disparity innovation insight loss of function men minimally invasive mortality neoplastic neoplastic cell outcome forecast racial difference research study tumor tumor initiation tumor progression

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer (PCa) disproportionally affects African American men (AA) who have 60 percent higher incidence rate and twice the death rate of Caucasian men (CA), and is the second leading cause of cancer- related deaths in AA men probably due to a more aggressive disease. While socioeconomic factors contribute to this health disparity, they do not fully explain the differences in prostate cancer incidence, aggressiveness, and mortality among different ethnic groups. Non-coding RNAs, especially, miRNAs have emerged for their important gene regulatory function and their roles in regulating multiple coding genes and thereby modulate several biological pathways including cell proliferation, differentiation, apoptosis, metastasis and angiogenesis. Recent studies have identified distinct miRNA expression in serum of cancer patients and have suggested their usefulness as molecular targets and as biomarkers to predict progression from preneoplasia to cancer and outcome/prognosis of cancer patients. Very little is known about racial differences in the expression of these miRNA in cancers like prostate cancer that disproportionally affect AA men. Based on our preliminary data, we hypothesize that miRNA dysregulation in serum might be associated with PCa progression and PCa health disparities with potential to be developed as molecular target(s) and minimally invasive biomarker(s). The specific aims are: (1) Study the expression of miR-101, miR-25 and miR-628-5p in prostate cancer where we will compare the expression of these miRNAs in (a) serum from 50 AA and 50 CA and (b) tissues from 50 AA and 50 CA prostate cancer patients by Q-PCR. (2) Examine the effects of miR-101, miR-25 and miR-628-5p gain- and loss-of-function on the neoplastic phenotype of prostate cancer and their oncogenic activity in normal prostate cells. This proposal will (i) establish a basis to study the expression pattern of these miRNAs in diverse serum samples and (ii) generate preliminary data for continued mechanistic investigation of miRNA biology in prostate cancer health disparities. Our future studies will validate these miRNAs in a wider population and examine the involvement of these miRNAs in the tumor biology of AA prostate cancer.

描述（由申请人提供）：前列腺癌 (PCa) 不成比例地影响非裔美国男性 (AA)，其发病率比白人男性 (CA) 高 60%，死亡率是白人男性 (CA) 的两倍，是癌症相关死亡的第二大原因在 AA 男性中，可能是由于一种更具侵袭性的疾病。虽然社会经济因素导致了这种健康差异，但它们并不能完全解释不同种族群体之间前列腺癌发病率、侵袭性和死亡率的差异。非编码RNA，尤其是miRNA，因其重要的基因调节功能及其在调节多个编码基因中的作用而出现，从而调节包括细胞增殖、分化、凋亡、转移和血管生成在内的多种生物途径。最近的研究已经确定了癌症患者血清中不同的 miRNA 表达，并表明它们可作为分子靶标和生物标志物来预测从肿瘤前期到癌症的进展以及癌症患者的结果/预后。人们对这些 miRNA 在癌症（如前列腺癌）中表达的种族差异知之甚少，而前列腺癌对 AA 男性的影响尤为严重。根据我们的初步数据，我们假设血清中的 miRNA 失调可能与 PCa 进展和 PCa 健康差异有关，有可能被开发为分子靶点和微创生物标志物。具体目标是：(1) 研究前列腺癌中 miR-101、miR-25 和 miR-628-5p 的表达，我们将比较这些 miRNA 在 (a) 50 个 AA 和 50 个 CA 的血清中的表达和 ( b) 通过 Q-PCR 检测 50 名 AA 和 50 名 CA 前列腺癌患者的组织。 (2) 检查 miR-101、miR-25 和 miR-628-5p 功能获得和丧失对前列腺癌肿瘤表型的影响及其在正常前列腺细胞中的致癌活性。该提案将 (i) 为研究这些 miRNA 在不同血清样本中的表达模式奠定基础，并 (ii) 为继续对前列腺癌健康差异中的 miRNA 生物学机制进行研究生成初步数据。我们未来的研究将在更广泛的人群中验证这些 miRNA，并检查这些 miRNA 在 AA 前列腺癌肿瘤生物学中的参与情况。