乳腺癌相关microRNA高灵敏检测的信号放大与传感新策略

MicroRNAs are a series of regulatory molecules that play crucial roles in a diverse range of biological processes. They can stably exist in the environment of ribonuclease, RNase. Their expression patterns are associated with various diseases, such as cancers. Thus they possess the potential superiority as biomarkers. The very low abundance, short and similar sequences of microRNAs bring a great challenge to their detection. Focussing on the application problems of existing microRNA detection methods in clinical diagnosis, this project will integrate the advantages of several nanomaterials, the specific recognition of molecular beacons and locked nucleic acid, the catalysis of DNA mimic enzymes, and a series of molecular biological technologies to design new multifunctional nanoprobes with unique optical or electrochemical properties and novel strategies for molecular biological signal amplification, and establish several rapid, sensitive, specific and label-free sensing methods and on site detection techniques for microRNA analysis. This project will further use the proposed methods to detect the microRNAs in circulating plasma, tissue and live cells from breast cancer patients for revealing the relation between microRNAs and occurrence as well as development of breast cancer and providing the breast cancer-related biomarkers for early diagnosis, treatment and prognosis. This research will innovatively present new methods for highly sensitive detection of cancer-related microRNA and promote the development of microRNA function study and relative diagnosis technology.

MicroRNA是一类在生命过程中起重要作用的调控分子，在富含核糖核酸酶RNase的环境中稳定存在，其表达与人类很多疾病（如癌症）密切相关，具有作为生物标志物的潜在优势。由于microRNA含量低、序列短且相似性高，其检测方法具有很大挑战性。针对现有microRNA检测方法难以在临床应用的问题，本项目将新型纳米材料、分子信标与锁核酸的选择性识别、DNA模拟酶催化反应和一系列新的分子生物学技术有机集合，设计性能优良的新型光电纳米探针和分子生物学信号放大新策略，建立快速、灵敏、特异、免标记的microRNA传感新方法，构建microRNA原位检测新技术，并用于乳腺癌microRNA检测，揭示它们与乳腺癌发生与发展的关系，为乳腺癌的诊断、治疗和预后评估提出相关标志物。本项目的实施将创新性地提出肿瘤相关microRNA的高灵敏检测新方法，促进microRNA功能研究及相关诊断技术的发展。

MicroRNA是一类在生命过程中起重要作用的调控分子，在富含核糖核酸酶RNase的环境中稳定存在，其表达与人类很多疾病（如癌症）密切相关，具有作为生物标志物的潜在优势。由于microRNA含量低、序列短且相似性高，其检测方法具有很大挑战性。针对现有microRNA检测方法难以在临床应用的问题，本项目制备探针、构建反应体系，创建了锁核酸分子信标高灵敏检测新策略，完成miR-145、miR-199a-5p 、miR-200c-3p、UHRF1、MALAT1检测，提出乳腺癌的诊断、治疗和预后评估的分子标志物。本项目申请国家发明专利2项；发表论文11篇（其中SCI刊物7篇）。项目执行期间，主持人被评为江苏省 “科教强卫工程”创新团队领军人才，获江苏省科学技术三等奖（排名第1）、江苏省医学新技术引进一等奖（排名第1）。应邀在World Congress on Oncology and Prevention Methods（2015, 迪拜）、Cancer Diagnositic（2016，意大利）、4th World Congress on Breast Pathology and Cancer Diagnosis（2017, 加拿大）、World Congress on Biomakers and Clinical Research（2017美国）做学术报告。培养硕士研究生7名，其中1名获得美国迈阿密医学院全额奖学金资助攻读博士学位（2015年）。本项目建立了肿瘤标志物研究技术平台，研究成果在国内外产生了良好的社会影响；本项目的完成在肿瘤标志物检测新技术创新方面具有重要价值。