Journal
CANCER CELL
Volume 31, Issue 4, Pages 576-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.03.004
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Funding
- 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
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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.
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