申请人现为美国克利夫兰临床中心教授，长期致力于非编码RNA特别是microRNA在恶性肿瘤发生发展过程中的功能和机制研究，在多项美国NIH RO1等课题资助下，近年来已在Cell Res、PNAS和Oncogene等期刊发表研究论文40余篇，论文被引用1600余次，2012年起受聘为中南大学客座教授，已与国内合作者团队联合培养了2名研究生，共同发表了7篇论文。本项目将以c-Myc高表达的髓母细胞瘤亚型为主要研究模型，深入探讨利用小分子药物二甲双胍和洛伐他汀上调miR-33的表达，并通过miR-33靶向抑制c-Myc，从而抑制髓母细胞瘤生长和转移的作用及其中的具体分子机制。本项目的完成不仅将揭示小分子药物对miR-33/c-Myc的表达调控原理，明晰miR-33和c-Myc在肿瘤发病中的作用机制，还可为临床上已广泛使用的降糖(二甲双胍)和降脂(洛伐他汀)药物开发抗肿瘤新用途提供实验依据。

The applicant, Dr. Yong Li, is a professor of Cleveland Clinic. He has long-term research experience in the functions and mechanisms of non-coding RNAs, especially miRNAs, in human carcinogenesis. His work is supported by multiple grants from the National Institute of Health of United State of America, etc. Dr. Li has published more than forty papers in various high impact peer-reviewed journals, including Cell Research, PNAS and Oncogene. His articles have been cited more than 1600 times. Professor Li is also a guest professor of Central South University and has collaborated with Dr. Zhaoyang Zeng and her team since 2012. Drs. Li and Zeng have jointly trained two graduate students and published 7 articles together. The proposed project will focus on a subtype of medulloblastoma that has high expression of c-Myc. Drs. Li and Zeng’s team will investigate the functions and mechanisms of small molecule drugs, metformin and lovastatin, on inducing the expression of miR-33. The induced miR-33 inhibits its target gene c-Myc, and ultimately suppresses the growth and metastasis of medulloblastoma. This project will reveal the regulation mechanism between small molecule drugs and the expression of miR-33 and c-Myc, which will further our understanding on their function in human cancer progression. Moreover, it will provide experimental evidence to support the repurposing of two FDA approved and wildly used drugs, metformin (a glucose suppressing drug for treatment of type 2 diabetes) and lovastatin (an antihyperlipidemic agents used for lowering cholesterol) as potential therapeutic agents for cancer treatment.

本项目以c-Myc高表达的髓母细胞瘤亚型为主要研究模型，深入探讨利用小分子药物二甲双胍和洛伐他汀上调miR-33的表达，并通过miR-33靶向抑制c-Myc，从而抑制髓母细胞瘤生长和转移的作用及其中的具体分子机制。初步揭示了小分子药物对miR-33/c-Myc的表达调控原理，明晰了miR-33和c-Myc在肿瘤发病中的作用机制，为临床上已广泛使用的降糖(二甲双胍)和降脂(洛伐他汀)药物开发抗肿瘤新用途提供实验依据。