Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers
Name
nihms860727.pdf
Description
Accepted version
Size
1.36 MB
Format
Adobe PDF
Checksum (MD5)
9ab231f87a461f656281b14910df8c16
Author(s)
Hydbring, Per
Wang, Yinan
Fassl, Anne
Li, Xiaoting
Matia, Veronica
Otto, Tobias
Choi, Yoon Jong
Sweeney, Katharine E.
Suski, Jan M.
Yin, Hao
Date Issued
April 2017
Journal
Cancer Cell
Publisher
Elsevier BV
Citation
Hydbring, Per et al. "Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers." Cancer Cell 31, 4 (April 2017): 576-590 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
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. Keywords: cell cycle; cyclins; cyclin-dependent kinases; microRNAs; cancers
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CCELL.2017.03.004
