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）：这是伊利诺伊大学芝加哥大学病理学助理教授Larisa Nonn博士的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，预防前列腺癌的博士后培训，并且刚刚转变为她的第一个独立位置。为了确保这一建议和她的职业生涯的成功，Nonn博士将自己置于支持性研究环境中，富含高级癌症预防研究人员。 该提案将识别并表征正常前列腺中维生素D调节的microRNA。现在很明显，调节性小型非编码microRNA（miRNA）在癌症发病机理中的作用显而易见。与蛋白质编码基因相似，已经鉴定出致癌miRNA和肿瘤抑制miRNA。我们假设化学预防剂，例如维生素D，以与癌症相关的miRNA变化的方式改变miRNA的表达。流行病学和实验室研究支持维生素D在前列腺中的化学预防作用。迄今为止，尚未研究维生素D或任何化学预防剂对miRNA的调节。 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/或潜在的致癌miRNA的下调。为了支持我们的假设，我们介绍了366 miRNA表达阵列的初步数据，表明维生素D调节了几种与前列腺癌相关的miRNA的表达。该建议将在这些令人兴奋的初步发现上扩展，并测试以下特定假设。 1）维生素D治疗正常人前列腺上皮细胞的原代培养物改变了前列腺癌相关的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miRNAS的表达与维生素D的浓度与维生素D的浓度相关。该提案的结果将基于基于确定的维生素D调节的miRNA为后续研究奠定基础。

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