2. Academic Validation
  3. Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers

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

  • Cancer Cell. 2017 Apr 10;31(4):576-590.e8. doi: 10.1016/j.ccell.2017.03.004.
Per Hydbring 1,  Yinan Wang 2,  Anne Fassl 3,  Xiaoting Li 4,  Veronica Matia 3,  Tobias Otto 3,  Yoon Jong Choi 3,  Katharine E Sweeney 3,  Jan M Suski 3,  Hao Yin 5,  Roman L Bogorad 5,  Shom Goel 6,  Haluk Yuzugullu 7,  Kevin J Kauffman 5,  Junghoon Yang 5,  Chong Jin 2,  Yingxiang Li 8,  Davide Floris 3,  Richard Swanson 9,  Kimmie Ng 10,  Ewa Sicinska 11,  Lars Anders 12,  Jean J Zhao 7,  Kornelia Polyak 13,  Daniel G Anderson 14,  Cheng Li 15,  Piotr Sicinski 16
Affiliations

Affiliations

  • 1 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02215, USA; Department of Oncology-Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.
  • 2 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Center for Life Sciences and Center for Statistical Science, Peking University, Beijing 100871, China.
  • 3 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
  • 4 School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 5 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • 6 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • 7 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • 8 Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
  • 9 Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • 10 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • 11 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • 12 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • 13 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • 14 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • 15 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Center for Life Sciences and Center for Statistical Science, Peking University, Beijing 100871, China. Electronic address: [email protected].
  • 16 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02215, USA. Electronic address: [email protected].
PMID: 28399412 DOI: 10.1016/j.ccell.2017.03.004
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

cancers; cell cycle; cyclin-dependent kinases; cyclins; microRNAs.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50767
    99.96%, CDK4/6 Inhibitor
    CDK