Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers | |
Hydbring, Per ; Wang, Yinan ; Fassl, Anne ; Li, Xiaoting ; Matia, Veronica ; Otto, Tobias ; Choi, Yoon Jong ; Sweeney, Katharine E. ; Suski, Jan M. ; Yin, Hao ; Bogorad, Roman L. ; Goel, Shom ; Yuzugullu, Haluk ; Kauffman, Kevin J. ; Yang, Junghoon ; Jin, Chong ; Li, Yingxiang ; Floris, Davide ; Swanson, Richard ; Ng, Kimmie ; Sicinska, Ewa ; Anders, Lars ; Zhao, Jean J. ; Polyak, Kornelia ; Anderson, Daniel G. ; Li, Cheng ; Sicinski, Piotr | |
2017 | |
关键词 | BREAST-CANCER TUMOR-SUPPRESSOR SYNTHETIC LETHAL PROSTATE-CANCER MIR-193A-3P MYC TUMORIGENESIS PROGRESSION METASTASIS INHIBITION |
英文摘要 | Cyclins and cyclin-dependent kinases (CDKs) are hyperactivated in numerous human tumors. To identify means of interfering with cyclins/CDKs, we performed nine genome-wide screens for human microRNAs (miRNAs) directly regulating cell-cycle proteins. We uncovered a distinct class of miRNAs that target nearly all cyclins/CDKs, which are very effective in inhibiting cancer cell proliferation. By profiling the response of over 120 human cancer cell lines, we derived an expression-based algorithm that can predict the response of tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we inhibited tumor progression in seven mouse xenograft models, including three treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cellcycle- targeting miRNAs for treatment of refractory cancer types.; NIH [5 R01 CA083688, 5 R01 CA132740, 5 P01 CA080111]; Wennergren Foundations (Stockholm, Sweden); Peking-Tsinghua Center for Life Sciences; National Natural Science Foundation of China [71532001]; MNISW Fellowship; Novartis; SCI(E); ARTICLE; 4; 576-+; 31 |
语种 | 英语 |
出处 | SCI |
出版者 | CANCER CELL |
内容类型 | 其他 |
源URL | [http://hdl.handle.net/20.500.11897/474050] |
专题 | 数学科学学院 生命科学学院 |
推荐引用方式 GB/T 7714 | Hydbring, Per,Wang, Yinan,Fassl, Anne,et al. Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. 2017-01-01. |
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