Significance of Vitamin D-Regulated MicroRNAs in Prostate Cancer Prevention

维生素 D 调控的 MicroRNA 在预防前列腺癌中的意义

• 批准号: 8082746
• 负责人: LARISA NONN
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-02 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8082746
• 关键词: Apoptosis; Area; Binding; Bioinformatics; Biological Assay; Blinded; Cancer Biology; Cell Line; Cells; Chemopreventive Agent; Chicago; Clinical; Code; Data; Down-Regulation; Ensure; Environment; Epidemiologic Studies; Epithelial Cells; Foundations; Freezing; Functional RNA; Gene Expression; Genes; Human; Illinois; Immigration; Individual; Laboratory Study; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Messenger RNA; MicroRNAs; Molecular Profiling; Oncogenic; Pathogenesis; Pathology; Patients; Pharmacology; Phenotype; Physiological; Positioning Attribute; Preventive; Primary Cell Cultures; Prostate; Prostatic; Proteins; Regulation; Reporting; Research; Research Personnel; Research Proposals; Role; Serum; Specimen; Testing; Tissues; Transfection; Transition Career Development Award (K22); Translations; Tumor Suppressor Proteins; Universities; Untranslated Regions; Up-Regulation; Vitamin D; Vitamin D2; Vitamins; base; cancer cell; cancer prevention; career; hormone refractory prostate cancer; mRNA Stability; post-doctoral training; professor; programs; prostate cancer prevention; prostate carcinogenesis; receptor; success

DESCRIPTION (provided by applicant): This is a NCI Transition Career Development Award (K22) proposal by Dr. Larisa Nonn, an Assistant Professor of Pathology at the University of Illinois at Chicago. She has a doctoral degree in Pharmacology/Cancer Biology, postdoctoral training in prostate cancer prevention and has just transitioned into her first independent position. To ensure success with this proposal and her career, Dr. Nonn has placed herself in a supportive research environment, rich in senior cancer prevention investigators. This proposal will identify and characterize vitamin D-regulated microRNAs in normal prostate. The role of regulatory small non-coding microRNAs (miRNAs) in the pathogenesis of cancer is now evident. Similarly to protein-coding genes, oncogenic miRNAs and tumor suppressor miRNAs have been identified. We postulate that chemopreventive agents, such as vitamin D, alter miRNA expression in a manner opposing to the cancer-associated miRNA changes. Epidemiologic and laboratory studies support a chemopreventive role for vitamin D in prostate. To date, regulation of miRNAs by vitamin D, or any chemopreventive agent, have not yet been investigated. Our overall hypothesis is that the prostate cancer preventive activities of vitamin D involve up-regulation of tumor suppressor miRNAs and/or down-regulation of potentially oncogenic miRNAs. In support of our hypothesis, we present preliminary data from a 366 miRNA expression array, showing that vitamin D regulates the expression of several prostate cancer-related miRNAs This proposal will expand on these exciting preliminary findings and test the following specific hypotheses; 1) vitamin D treatment of primary cultures of normal human prostatic epithelial cells alters the expression of prostate cancer-related miRNAs, 2) vitamin D-regulated miRNAs exert anti-cancer activity in prostate cells, and 3) the expression of vitamin D-regulated miRNAs correlate with the concentration of vitamin D metabolites in prostate tissue. The results of this proposal will lay the foundation for subsequent studies based on the identified vitamin D-regulated miRNAs.

描述（由申请人提供）：这是由芝加哥伊利诺伊大学病理学助理教授 Larisa Nonn 博士提出的 NCI 过渡职业发展奖 (K22) 提案。她拥有药理学/癌症生物学博士学位，接受过前列腺癌预防的博士后培训，并且刚刚过渡到她的第一个独立职位。为了确保这一提案和她的职业生涯取得成功，Nonn 博士将自己置于一个拥有丰富的高级癌症预防研究人员的支持性研究环境中。 该提案将鉴定并表征正常前列腺中维生素 D 调节的 microRNA。调节性小非编码 microRNA (miRNA) 在癌症发病机制中的作用现已显而易见。与蛋白质编码基因类似，致癌 miRNA 和抑癌 miRNA 也已被鉴定。我们假设化学预防剂（例如维生素 D）以与癌症相关 miRNA 变化相反的方式改变 miRNA 表达。流行病学和实验室研究支持维生素 D 对前列腺具有化学预防作用。迄今为止，维生素 D 或任何化学预防剂对 miRNA 的调节尚未得到研究。 我们的总体假设是，维生素 D 的前列腺癌预防活性涉及肿瘤抑制 miRNA 的上调和/或潜在致癌 miRNA 的下调。为了支持我们的假设，我们提供了来自 366 个 miRNA 表达阵列的初步数据，表明维生素 D 调节几种前列腺癌相关 miRNA 的表达。该提案将扩展这些令人兴奋的初步发现，并测试以下具体假设； 1) 正常人前列腺上皮细胞原代培养物的维生素 D 处理改变了前列腺癌相关 miRNA 的表达，2) 维生素 D 调节的 miRNA 在前列腺细胞中发挥抗癌活性，3) 维生素 D 调节的 miRNA 的表达与前列腺组织中维生素 D 代谢物的浓度相关。该提案的结果将为后续基于已鉴定的维生素 D 调控 miRNA 的研究奠定基础。

项目成果

Tumor suppressor microRNAs, miR-100 and -125b, are regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in patient tissue.

• DOI: 10.1158/1940-6207.capr-12-0253
• 发表时间: 2013-05
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Giangreco AA;Vaishnav A;Wagner D;Finelli A;Fleshner N;Van der Kwast T;Vieth R;Nonn L
• 通讯作者: Nonn L

Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.

• DOI: 10.1016/j.jsbmb.2014.10.004
• 发表时间: 2015-04
• 期刊: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
• 影响因子: 4.1
• 作者: Giangreco, Angeline A.;Dambal, Shweta;Wagner, Dennis;Van der Kwast, Theodorus;Vieth, Reinhold;Prins, Gail S.;Nonn, Larisa
• 通讯作者: Nonn, Larisa

The sum of many small changes: microRNAs are specifically and potentially globally altered by vitamin D3 metabolites.

• DOI: 10.1016/j.jsbmb.2013.01.001
• 发表时间: 2013-07
• 期刊: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
• 影响因子: 4.1
• 作者: Giangreco, Angeline A.;Nonn, Larisa
• 通讯作者: Nonn, Larisa

microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma.

• DOI: 10.1016/j.jsbmb.2017.01.004
• 发表时间: 2017-03
• 期刊: The Journal of steroid biochemistry and molecular biology
• 作者: Dambal S;Giangreco AA;Acosta AM;Fairchild A;Richards Z;Deaton R;Wagner D;Vieth R;Gann PH;Kajdacsy-Balla A;Van der Kwast T;Nonn L
• 通讯作者: Nonn L