Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice
Integrins play an important role during development, regulating cell differentiation, proliferation and survival. Here we show that knockdown of integrin subunits slows down the progression of hepatocellular carcinoma (HCC). Using nanoparticulate delivery of short interfering RNAs targeting β1 and α...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/101131 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 |
| _version_ | 1826214038388867072 |
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| author | Yin, Hao Zeigerer, Anja Nonaka, Hidenori Zerial, Marino Koteliansky, Victor Anderson, Daniel Griffith Ruda, Vera Bogorad, Roman |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Yin, Hao Zeigerer, Anja Nonaka, Hidenori Zerial, Marino Koteliansky, Victor Anderson, Daniel Griffith Ruda, Vera Bogorad, Roman |
| author_sort | Yin, Hao |
| collection | MIT |
| description | Integrins play an important role during development, regulating cell differentiation, proliferation and survival. Here we show that knockdown of integrin subunits slows down the progression of hepatocellular carcinoma (HCC). Using nanoparticulate delivery of short interfering RNAs targeting β1 and αv integrin subunits, we downregulate all integrin receptors in hepatocytes. Short-term integrin knockdown (2 weeks) does not cause apparent structural or functional perturbations of normal liver tissue. Alterations in liver morphology accumulate on sustained integrin downregulation (7 weeks). The integrin knockdown leads to significant retardation of HCC progression, reducing proliferation and increasing tumour cell death. This tumour retardation is accompanied by reduced activation of the MET oncogene as well as expression of its mature form on the cell surface. Our data suggest that transformed proliferating cells from HCC are more sensitive to knockdown of integrins than normal quiescent hepatocytes, highlighting the potential of small interfering RNA-mediated inhibition of integrins as an anti-cancer therapeutic approach. |
| first_indexed | 2024-09-23T15:58:49Z |
| format | Article |
| id | mit-1721.1/101131 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:58:49Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1011312022-10-02T05:30:18Z Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice Yin, Hao Zeigerer, Anja Nonaka, Hidenori Zerial, Marino Koteliansky, Victor Anderson, Daniel Griffith Ruda, Vera Bogorad, Roman Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Bogorad, Roman L. Yin, Hao Ruda, Vera M. Anderson, Daniel Griffith Koteliansky, Victor Integrins play an important role during development, regulating cell differentiation, proliferation and survival. Here we show that knockdown of integrin subunits slows down the progression of hepatocellular carcinoma (HCC). Using nanoparticulate delivery of short interfering RNAs targeting β1 and αv integrin subunits, we downregulate all integrin receptors in hepatocytes. Short-term integrin knockdown (2 weeks) does not cause apparent structural or functional perturbations of normal liver tissue. Alterations in liver morphology accumulate on sustained integrin downregulation (7 weeks). The integrin knockdown leads to significant retardation of HCC progression, reducing proliferation and increasing tumour cell death. This tumour retardation is accompanied by reduced activation of the MET oncogene as well as expression of its mature form on the cell surface. Our data suggest that transformed proliferating cells from HCC are more sensitive to knockdown of integrins than normal quiescent hepatocytes, highlighting the potential of small interfering RNA-mediated inhibition of integrins as an anti-cancer therapeutic approach. Alnylam Pharmaceuticals (Firm) National Institutes of Health (U.S.) (RO1-DE016516) National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30CCA14051) 2016-02-09T15:47:11Z 2016-02-09T15:47:11Z 2014-05 2013-12 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/101131 Bogorad, Roman L., Hao Yin, Anja Zeigerer, Hidenori Nonaka, Vera M. Ruda, Marino Zerial, Daniel G. Anderson, and Victor Koteliansky. “Nanoparticle-Formulated siRNA Targeting Integrins Inhibits Hepatocellular Carcinoma Progression in Mice.” Nat Comms 5 (May 21, 2014). https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 en_US http://dx.doi.org/10.1038/ncomms4869 Nature Communications Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Yin, Hao Zeigerer, Anja Nonaka, Hidenori Zerial, Marino Koteliansky, Victor Anderson, Daniel Griffith Ruda, Vera Bogorad, Roman Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title | Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title_full | Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title_fullStr | Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title_full_unstemmed | Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title_short | Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice |
| title_sort | nanoparticle formulated sirna targeting integrins inhibits hepatocellular carcinoma progression in mice |
| url | http://hdl.handle.net/1721.1/101131 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 |
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