Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma
MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (26), p.E1695-E1704 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Babar, Imran A Cheng, Christopher J Booth, Carmen J Liang, Xianping Weidhaas, Joanne B Saltzman, W. Mark Slack, Frank J |
| description | MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these “addicted” pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia. |
| doi_str_mv | 10.1073/pnas.1201516109 |
| format | Article |
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We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these “addicted” pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1201516109</identifier><identifier>PMID: 22685206</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>animal models ; Animals ; Apoptosis ; Base Sequence ; Biological Sciences ; Blotting, Western ; Cell division ; Correlation analysis ; Disease Models, Animal ; DNA Primers ; Doxycycline - pharmacology ; Flow Cytometry ; immunomodulation ; leukemia ; lymphocytes ; Lymphoid Tissue - metabolism ; lymphoma ; Lymphoma - genetics ; Lymphoma - pathology ; Lymphoma - therapy ; Mice ; microRNA ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - biosynthesis ; Nanoparticles ; PNAS Plus ; Polymerase Chain Reaction ; polymers ; prognosis ; Ribonucleic acid ; RNA ; Rodents ; therapeutics ; tissues ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-06, Vol.109 (26), p.E1695-E1704</ispartof><rights>Copyright National Academy of Sciences Jun 26, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-104c3c1f99a393433d6b263c5ff2dd40a2905d44305c4897aa0240187fe64d1c3</citedby><cites>FETCH-LOGICAL-c569t-104c3c1f99a393433d6b263c5ff2dd40a2905d44305c4897aa0240187fe64d1c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/26.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387084/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387084/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22685206$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Babar, Imran A</creatorcontrib><creatorcontrib>Cheng, Christopher J</creatorcontrib><creatorcontrib>Booth, Carmen J</creatorcontrib><creatorcontrib>Liang, Xianping</creatorcontrib><creatorcontrib>Weidhaas, Joanne B</creatorcontrib><creatorcontrib>Saltzman, W. Mark</creatorcontrib><creatorcontrib>Slack, Frank J</creatorcontrib><title>Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these “addicted” pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.</description><subject>animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>Cell division</subject><subject>Correlation analysis</subject><subject>Disease Models, Animal</subject><subject>DNA Primers</subject><subject>Doxycycline - pharmacology</subject><subject>Flow Cytometry</subject><subject>immunomodulation</subject><subject>leukemia</subject><subject>lymphocytes</subject><subject>Lymphoid Tissue - metabolism</subject><subject>lymphoma</subject><subject>Lymphoma - genetics</subject><subject>Lymphoma - pathology</subject><subject>Lymphoma - therapy</subject><subject>Mice</subject><subject>microRNA</subject><subject>MicroRNAs - antagonists & inhibitors</subject><subject>MicroRNAs - biosynthesis</subject><subject>Nanoparticles</subject><subject>PNAS Plus</subject><subject>Polymerase Chain Reaction</subject><subject>polymers</subject><subject>prognosis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>therapeutics</subject><subject>tissues</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1r3DAQxUVpabZpz721hl6Sg5PRp6VLIYS0KYQE8nEWWknOKtiWK3kX9r-vzG6TNpeRQL95M08Poc8YTjA09HQcTD7BBDDHAoN6gxal4lowBW_RAoA0tWSEHaAPOT8BgOIS3qMDQoTkBMQCmWszxNGkKdjO10uTvaumlU9m3FZhqMww103YxKoPNsXb67Mac14d9eF2vhzXzo9-cH6Yqj6usy_V-a6KbdVt-3EVe_MRvWtNl_2n_XmIHn5c3J9f1lc3P3-dn13Vlgs11RiYpRa3ShmqKKPUiSUR1PK2Jc4xMEQBd4xR4JZJ1RgDhAGWTesFc9jSQ_R9pzuul713tqyUTKfHFHqTtjqaoP9_GcJKP8aNplQ2IFkRONoLpPh77fOk-5Ct7zoz-GJNYwkUC8Y4Lui3V-hTXKeh2NMYCGFNwxgU6nRHlY_LOfn2eRkMeo5Pz_Hpl_hKx5d_PTzzf_MqQLUH5s4XOaWJ0BdYKF6QrzukNVGbxxSyfrgrIwQAJlIyRf8AT7Sn5A</recordid><startdate>20120626</startdate><enddate>20120626</enddate><creator>Babar, Imran A</creator><creator>Cheng, Christopher J</creator><creator>Booth, Carmen J</creator><creator>Liang, Xianping</creator><creator>Weidhaas, Joanne B</creator><creator>Saltzman, W. 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Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these “addicted” pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22685206</pmid><doi>10.1073/pnas.1201516109</doi><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | animal models Animals Apoptosis Base Sequence Biological Sciences Blotting, Western Cell division Correlation analysis Disease Models, Animal DNA Primers Doxycycline - pharmacology Flow Cytometry immunomodulation leukemia lymphocytes Lymphoid Tissue - metabolism lymphoma Lymphoma - genetics Lymphoma - pathology Lymphoma - therapy Mice microRNA MicroRNAs - antagonists & inhibitors MicroRNAs - biosynthesis Nanoparticles PNAS Plus Polymerase Chain Reaction polymers prognosis Ribonucleic acid RNA Rodents therapeutics tissues Tumors |
| title | Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma |
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