NamiRNA正向调控G蛋白偶联雌激素受体表达在乳腺癌发病中 ...
NamiRNA正向调控G蛋白偶联雌激素受体表达在乳腺癌发病中 ...
- 导航：首页 > 科学基金
- 批准号：31671308
- 批准年度：2016年
- 学科分类：遗传与变异（C060406） |
- 项目负责人：于文强
- 负责人职称：研究员
- 依托单位：复旦大学
- 资助金额：62万元
- 项目类别：面上项目
- 研究期限：2017年01月01日 至 2020年12月31日
- 中文关键词：NamiRNA；偶联；雌激素受体；乳腺癌；发病
- 英文关键词：Nuclear Activating miRNA;Enhancer;Transcriptional activation;Breast Cancer;Non Coding RNA
项目摘要
中文摘要
miRNA传统上在细胞浆中通过结合靶基因3’UTR抑制翻译或降解mRNA进而发挥负向调控作用，这很难解释许多定位于细胞核内miRNA作用机制。肿瘤相关miRNA低表达是肿瘤细胞重要分子特征，而低表达miRNA如何精准调控肿瘤生物学行为仍面临诸多挑战。我们前期研究工作发现定位于细胞核内miRNA与公认的miRNA在胞浆中负向调控机制不同，可通过结合增强子序列进而发挥基因转录激活作用，命名为NamiRNA （Nuclear Activating miRNA）。本项目以乳腺癌低表达miRNA与潜在靶基因为研究对象，确定乳腺癌中低表达miR-339改变增强子活性与GPER1正向调控关系，力图阐明miR-339对GPER1正向调控分子机制，探讨miR-339对GPER1正向调控对乳腺癌细胞生物学行为影响，从全新角度诠释肿瘤相关miRNA在乳腺癌发生发展中的作用，寻找miRNA干预对乳腺癌治疗新策略。
英文摘要
MicroRNAs (miRNAs) are small non-coding RNAs that canonically inhibit the translation or promote degradation messenger RNAs (mRNAs) through an RNA-RNA interaction with the 3-untranslated region (UTR) of target genes in the cytoplasm. However, the function of abundant miRNAs in the nucleus remained unclear. Notably, it was found that miRNAs tend to have a lower expression in cancer, which is acknowledged as an important molecular characteristic of cancer cells. Yet many challenges remain to illustrate the mechanisms how biologic behavior of tumors is properly controlled by such low expression miRNAs. In our previous research, we found that the function of nuclear miRNAs is completely different from cytoplasmic miRNAs. In contrast to the negative regulation, the nuclear miRNAs could activate gene transcription by binding to enhancer regions, termed as NamiRNA (Nuclear Activating miRNA). Here, our current proposed project try to explore positive regulation of low expression miRNAs in breast cancer and focus on investigating the function of miR-339 in the regulation of enhancer activities and expression of GPER1. We will illuminate the mechanisms through which GPER1 gene expression is up regulated by miR-339, and further explore the function of miR-339 and GPER1 throughout each stage of breast cancer. In the end, we hope to uncover a new perspective towards understanding the function of tumor associated miRNAs in breast cancer development, and provide a new and effective strategy to inhibit breast cancer development through NamiRNA intervention.
评估说明
国家自然科学基金项目“NamiRNA正向调控G蛋白偶联雌激素受体表达在乳腺癌发病中作用研究”发布于爱科学iikx，并永久归类于相关科学基金导航中，仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划，以及科学技术发展方向，面向全国资助基础研究和应用研究，发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。