MiR-10b Downregulates the Stress-Induced Cell Surface Molecule MICB, a Critical Ligand for Cancer Cell Recognition by Natural Killer Cells
Natural killer cells (NK) are a component of innate immunity well known for their potent ability to kill virus-infected or neoplastically transformed cells following stimulation of the NK cell receptor NKG2D. One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2012-11, Vol.72 (21), p.5463-5472 |
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| creator | TSUKERMAN, Pinchas STERN-GINOSSAR, Noam LANKRY, Dikla MANDELBOIM, Ofer GUR, Chamutal GLASNER, Ariella NACHMANI, Daphna BAUMAN, Yoav YAMIN, Rachel VITENSHTEIN, Alon STANIETSKY, Noah BAR-MAG, Tomer |
| description | Natural killer cells (NK) are a component of innate immunity well known for their potent ability to kill virus-infected or neoplastically transformed cells following stimulation of the NK cell receptor NKG2D. One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to be upregulated on the surface of tumor cells. However, there is little knowledge about how this upregulation may occur or how it may be selected against in tumors as a mechanism of immune escape. Here, we report that the metastasis-associated microRNA (metastamir) miR-10b directly binds to the 3' untranslated region of MICB and downregulates its expression. Notably, antagonizing miR-10b action enhanced NKG2D-mediated killing of tumor cells in vitro and enhanced clearance of tumors in vivo. Conversely, overexpression of miR-10b downregulated MICB and impaired elimination of tumor cells. Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells. |
| doi_str_mv | 10.1158/0008-5472.can-11-2671 |
| format | Article |
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One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to be upregulated on the surface of tumor cells. However, there is little knowledge about how this upregulation may occur or how it may be selected against in tumors as a mechanism of immune escape. Here, we report that the metastasis-associated microRNA (metastamir) miR-10b directly binds to the 3' untranslated region of MICB and downregulates its expression. Notably, antagonizing miR-10b action enhanced NKG2D-mediated killing of tumor cells in vitro and enhanced clearance of tumors in vivo. Conversely, overexpression of miR-10b downregulated MICB and impaired elimination of tumor cells. Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells.</description><identifier>ISSN: 0008-5472</identifier><identifier>ISSN: 1538-7445</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-11-2671</identifier><identifier>PMID: 22915757</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Cell Line, Tumor ; Down-Regulation ; Gene Expression Regulation, Neoplastic - genetics ; Histocompatibility Antigens Class I - biosynthesis ; Histocompatibility Antigens Class I - genetics ; Histocompatibility Antigens Class I - immunology ; Humans ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Ligands ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; MicroRNAs - immunology ; MicroRNAs - metabolism ; Neoplasm Invasiveness - genetics ; Neoplasm Invasiveness - immunology ; Neoplasms - genetics ; Neoplasms - immunology ; Neoplasms - metabolism ; Pharmacology. 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Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Down-Regulation</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Histocompatibility Antigens Class I - biosynthesis</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Humans</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Ligands</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNAs - immunology</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neoplasm Invasiveness - immunology</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Tumor Escape - genetics</subject><subject>Tumor Escape - immunology</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi1ERaeFRwB5g9RFXWzHjuNlSbmMmBaphbV14pwMQZ6k2IlQX4GnxtFMyxJ54Yu-__jofIS8FvxCCF2945xXTCsjLzwMTAgmSyOekZXQRcWMUvo5WT0xx-QkpZ_5qgXXL8ixlFZoo82K_Lnub5ngDb0afw8Rt3OACROdfiC9myKmxNZDO3tsaY0h0Ls5duCRXo8B_RzyYV2_P6dA69hPvYdAN_0WhpZ2Y6Q1DB7jPniLftwOmRkH2jzQG5jmmOkvfQgHJL0kRx2EhK8O-yn5_vHDt_oz23z9tK4vN8zryk4MrC0a0LIyqiyUxVaVHIRtrZTeVFpYj50uGo6FEgCgva9a3njPjbFStVCckrN93fs4_poxTW7XJ587gAHHOTmhtSjz4ur_qJBlBrksMqr3qI9jShE7dx_7HcQHJ7hbjLnFhltsuPryJj-5xVjOvTl8MTc7bJ9Sj4oy8PYAQMoD7mKeap_-caW21dLBX-mrnXM</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>TSUKERMAN, Pinchas</creator><creator>STERN-GINOSSAR, Noam</creator><creator>LANKRY, Dikla</creator><creator>MANDELBOIM, Ofer</creator><creator>GUR, Chamutal</creator><creator>GLASNER, Ariella</creator><creator>NACHMANI, Daphna</creator><creator>BAUMAN, Yoav</creator><creator>YAMIN, Rachel</creator><creator>VITENSHTEIN, Alon</creator><creator>STANIETSKY, Noah</creator><creator>BAR-MAG, Tomer</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20121101</creationdate><title>MiR-10b Downregulates the Stress-Induced Cell Surface Molecule MICB, a Critical Ligand for Cancer Cell Recognition by Natural Killer Cells</title><author>TSUKERMAN, Pinchas ; STERN-GINOSSAR, Noam ; LANKRY, Dikla ; MANDELBOIM, Ofer ; GUR, Chamutal ; GLASNER, Ariella ; NACHMANI, Daphna ; BAUMAN, Yoav ; YAMIN, Rachel ; VITENSHTEIN, Alon ; STANIETSKY, Noah ; BAR-MAG, Tomer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-a993ba528746349ed460a19d922c78519cef53b0e341aaa5cc8d0bcc077924da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Down-Regulation</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Histocompatibility Antigens Class I - biosynthesis</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>Histocompatibility Antigens Class I - immunology</topic><topic>Humans</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs - immunology</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neoplasm Invasiveness - immunology</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Tumor Escape - genetics</topic><topic>Tumor Escape - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TSUKERMAN, Pinchas</creatorcontrib><creatorcontrib>STERN-GINOSSAR, Noam</creatorcontrib><creatorcontrib>LANKRY, Dikla</creatorcontrib><creatorcontrib>MANDELBOIM, Ofer</creatorcontrib><creatorcontrib>GUR, Chamutal</creatorcontrib><creatorcontrib>GLASNER, Ariella</creatorcontrib><creatorcontrib>NACHMANI, Daphna</creatorcontrib><creatorcontrib>BAUMAN, Yoav</creatorcontrib><creatorcontrib>YAMIN, Rachel</creatorcontrib><creatorcontrib>VITENSHTEIN, Alon</creatorcontrib><creatorcontrib>STANIETSKY, Noah</creatorcontrib><creatorcontrib>BAR-MAG, Tomer</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TSUKERMAN, Pinchas</au><au>STERN-GINOSSAR, Noam</au><au>LANKRY, Dikla</au><au>MANDELBOIM, Ofer</au><au>GUR, Chamutal</au><au>GLASNER, Ariella</au><au>NACHMANI, Daphna</au><au>BAUMAN, Yoav</au><au>YAMIN, Rachel</au><au>VITENSHTEIN, Alon</au><au>STANIETSKY, Noah</au><au>BAR-MAG, Tomer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MiR-10b Downregulates the Stress-Induced Cell Surface Molecule MICB, a Critical Ligand for Cancer Cell Recognition by Natural Killer Cells</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>72</volume><issue>21</issue><spage>5463</spage><epage>5472</epage><pages>5463-5472</pages><issn>0008-5472</issn><issn>1538-7445</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Natural killer cells (NK) are a component of innate immunity well known for their potent ability to kill virus-infected or neoplastically transformed cells following stimulation of the NK cell receptor NKG2D. One of the various ligands of NKG2D is MICB, a stress-induced ligand that has been found to be upregulated on the surface of tumor cells. However, there is little knowledge about how this upregulation may occur or how it may be selected against in tumors as a mechanism of immune escape. Here, we report that the metastasis-associated microRNA (metastamir) miR-10b directly binds to the 3' untranslated region of MICB and downregulates its expression. Notably, antagonizing miR-10b action enhanced NKG2D-mediated killing of tumor cells in vitro and enhanced clearance of tumors in vivo. Conversely, overexpression of miR-10b downregulated MICB and impaired elimination of tumor cells. Together, our results define MICB as a novel immune target of miR-10b, implying a direct link between metastasis capability and immune escape from NK cells.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>22915757</pmid><doi>10.1158/0008-5472.can-11-2671</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animals Antineoplastic agents Biological and medical sciences Cell Line, Tumor Down-Regulation Gene Expression Regulation, Neoplastic - genetics Histocompatibility Antigens Class I - biosynthesis Histocompatibility Antigens Class I - genetics Histocompatibility Antigens Class I - immunology Humans Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Ligands Male Medical sciences Mice Mice, Inbred C57BL MicroRNAs - immunology MicroRNAs - metabolism Neoplasm Invasiveness - genetics Neoplasm Invasiveness - immunology Neoplasms - genetics Neoplasms - immunology Neoplasms - metabolism Pharmacology. Drug treatments Real-Time Polymerase Chain Reaction Tumor Escape - genetics Tumor Escape - immunology Tumors |
| title | MiR-10b Downregulates the Stress-Induced Cell Surface Molecule MICB, a Critical Ligand for Cancer Cell Recognition by Natural Killer Cells |
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