Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.


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 cell-cycle-targeting miRNAs for treatment of refractory cancer types.

DOI: 10.1016/j.ccell.2017.03.004


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@article{Hydbring2017CellCycleTargetingMA, title={Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers.}, author={Per Hydbring and Yinan Wang and Anne Fassl and Xiaoting Li and Veronica Matia and Tobias Otto and Yoon Jong Choi and Katharine E Sweeney and Jan M Suski and Hao Yin and Roman L. Bogorad and Shom Goel and Haluk Yuzugullu and Kevin J. Kauffman and Junghoon Yang and Chong Wei Jin and Yingxiang Li and Davide Floris and Richard S. Swanson and Kimmie Ng and Ewa T. Sicinska and Lars Anders and Jean J. Zhao and Korn{\'e}lia Poly{\'a}k and Daniel G Anderson and Cheng Li and Piotr Sicinski}, journal={Cancer cell}, year={2017}, volume={31 4}, pages={576-590.e8} }