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

Per Hydbring; Yinan Wang; Anne Fassl; Xiaoting Li; Veronica Matia; Tobias Otto; Yoon Jong Choi; Katharine E. Sweeney; Jan M. Suski; Hao Yin; Roman L. Bogorad; Shom Goel; Haluk Yuzugullu; Kevin J. Kauffman; Junghoon Yang; Chong Jin; Yingxiang Li; Davide Floris; Richard Swanson; Kimmie Ng; Ewa Sicinska; Lars Anders; Jean J. Zhao; Kornelia Polyak; Daniel G. Anderson; Cheng Li; Piotr Sicinski

doi:10.1016/j.ccell.2017.03.004

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

Per Hydbring, Yinan Wang, Anne Fassl, Xiaoting Li, Veronica Matia, Tobias Otto, Yoon Jong Choi, Katharine E. Sweeney, Jan M. Suski, Hao Yin, Roman L. Bogorad, Shom Goel, Haluk Yuzugullu, Kevin J. Kauffman, Junghoon Yang, Chong Jin, Yingxiang Li, Davide Floris, Richard Swanson, Kimmie NgEwa Sicinska, Lars Anders, Jean J. Zhao, Kornelia Polyak, Daniel G. Anderson, Cheng Li, Piotr Sicinski

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

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.

Original language	English (US)
Pages (from-to)	576-590.e8
Journal	Cancer Cell
Volume	31
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2017.03.004
State	Published - Apr 10 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

Keywords

cancers
cell cycle
cyclin-dependent kinases
cyclins
microRNAs

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10.1016/j.ccell.2017.03.004

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Hydbring, P., Wang, Y., Fassl, A., Li, X., Matia, V., Otto, T., Choi, Y. J., Sweeney, K. E., Suski, J. M., Yin, H., Bogorad, R. L., Goel, S., Yuzugullu, H., Kauffman, K. J., Yang, J., Jin, C., Li, Y., Floris, D., Swanson, R., ... Sicinski, P. (2017). Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. Cancer Cell, 31(4), 576-590.e8. https://doi.org/10.1016/j.ccell.2017.03.004

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title = "Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers",

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",

author = "Per Hydbring and Yinan Wang and Anne Fassl and Xiaoting Li and Veronica Matia and Tobias Otto and Choi, {Yoon Jong} and Sweeney, {Katharine E.} and Suski, {Jan M.} and Hao Yin and Bogorad, {Roman L.} and Shom Goel and Haluk Yuzugullu and Kauffman, {Kevin J.} and Junghoon Yang and Chong Jin and Yingxiang Li and Davide Floris and Richard Swanson and Kimmie Ng and Ewa Sicinska and Lars Anders and Zhao, {Jean J.} and Kornelia Polyak and Anderson, {Daniel G.} and Cheng Li and Piotr Sicinski",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = apr,

day = "10",

doi = "10.1016/j.ccell.2017.03.004",

language = "English (US)",

volume = "31",

pages = "576--590.e8",

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Hydbring, P, Wang, Y, Fassl, A, Li, X, Matia, V, Otto, T, Choi, YJ, Sweeney, KE, Suski, JM, Yin, H, Bogorad, RL, Goel, S, Yuzugullu, H, Kauffman, KJ, Yang, J, Jin, C, Li, Y, Floris, D, Swanson, R, Ng, K, Sicinska, E, Anders, L, Zhao, JJ, Polyak, K, Anderson, DG, Li, C & Sicinski, P 2017, 'Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers', Cancer Cell, vol. 31, no. 4, pp. 576-590.e8. https://doi.org/10.1016/j.ccell.2017.03.004

TY - JOUR

T1 - Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers

AU - Hydbring, Per

AU - Wang, Yinan

AU - Fassl, Anne

AU - Li, Xiaoting

AU - Matia, Veronica

AU - Otto, Tobias

AU - Choi, Yoon Jong

AU - Sweeney, Katharine E.

AU - Suski, Jan M.

AU - Yin, Hao

AU - Bogorad, Roman L.

AU - Goel, Shom

AU - Yuzugullu, Haluk

AU - Kauffman, Kevin J.

AU - Yang, Junghoon

AU - Jin, Chong

AU - Li, Yingxiang

AU - Floris, Davide

AU - Swanson, Richard

AU - Ng, Kimmie

AU - Sicinska, Ewa

AU - Anders, Lars

AU - Zhao, Jean J.

AU - Polyak, Kornelia

AU - Anderson, Daniel G.

AU - Li, Cheng

AU - Sicinski, Piotr

PY - 2017/4/10

Y1 - 2017/4/10

N2 - 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.

AB - 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.

KW - cancers

KW - cell cycle

KW - cyclin-dependent kinases

KW - cyclins

KW - microRNAs

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UR - http://www.scopus.com/inward/citedby.url?scp=85017360607&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.03.004

DO - 10.1016/j.ccell.2017.03.004

M3 - Article

C2 - 28399412

AN - SCOPUS:85017360607

SN - 1535-6108

VL - 31

SP - 576-590.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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