HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway
Identifieur interne : 002B21 ( Main/Exploration ); précédent : 002B20; suivant : 002B22HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway
Auteurs : Min Xue [République populaire de Chine] ; Shuihong Yao [République populaire de Chine] ; Minmin Hu [République populaire de Chine] ; Wan Li [République populaire de Chine] ; Tingting Hao [République populaire de Chine] ; Feng Zhou [République populaire de Chine] ; Xiaofei Zhu [République populaire de Chine] ; Hongmei Lu [République populaire de Chine] ; Di Qin [République populaire de Chine] ; Qin Yan [République populaire de Chine] ; Jianzhong Zhu [États-Unis] ; Shou-Jiang Gao [États-Unis] ; Chun Lu [République populaire de Chine]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Carcinogenèse (métabolisme), Cellules endothéliales (cytologie), Cellules endothéliales (enzymologie), Cellules endothéliales (métabolisme), Embryon de poulet, Humains, Lignée cellulaire, Mâle, Néovascularisation physiologique, Phosphohydrolase PTEN (métabolisme), Produits du gène nef du virus de l'immunodéficience humaine (métabolisme), Prolifération cellulaire, Protéines proto-oncogènes c-akt (métabolisme), Protéines virales (métabolisme), Souris, Souris de lignée BALB C, Souris nude, Sérine-thréonine kinases TOR (métabolisme), Transduction du signal, microARN (biosynthèse), microARN (métabolisme).
- MESH :
- biosynthèse : microARN.
- cytologie : Cellules endothéliales.
- enzymologie : Cellules endothéliales.
- métabolisme : Carcinogenèse, Cellules endothéliales, Phosphohydrolase PTEN, Produits du gène nef du virus de l'immunodéficience humaine, Protéines proto-oncogènes c-akt, Protéines virales, Sérine-thréonine kinases TOR, microARN.
- Animaux, Embryon de poulet, Humains, Lignée cellulaire, Mâle, Néovascularisation physiologique, Prolifération cellulaire, Souris, Souris de lignée BALB C, Souris nude, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Carcinogenesis (metabolism), Cell Line, Cell Proliferation, Chick Embryo, Endothelial Cells (cytology), Endothelial Cells (enzymology), Endothelial Cells (metabolism), Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs (biosynthesis), MicroRNAs (metabolism), Neovascularization, Physiologic, PTEN Phosphohydrolase (metabolism), Proto-Oncogene Proteins c-akt (metabolism), Signal Transduction, TOR Serine-Threonine Kinases (metabolism), Viral Proteins (metabolism), nef Gene Products, Human Immunodeficiency Virus (metabolism).
- MESH :
- chemical , biosynthesis : MicroRNAs.
- cytology : Endothelial Cells.
- enzymology : Endothelial Cells.
- metabolism : Carcinogenesis, Endothelial Cells, MicroRNAs, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Viral Proteins, nef Gene Products, Human Immunodeficiency Virus.
- Animals, Cell Line, Cell Proliferation, Chick Embryo, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neovascularization, Physiologic, Signal Transduction.
Abstract
Kaposi's sarcoma (KS) is an AIDS-defining cancer with aberrant neovascularization caused by KS-associated herpesvirus (KSHV). Although the interaction between HIV-1 and KSHV plays a pivotal role in promoting the aggressive manifestations of KS, the pathogenesis underlying AIDS-KS remains largely unknown. Here we examined HIV-1 Nef protein promotion of KSHV oncoprotein K1-induced angiogenesis. We showed that both internalized and ectopic expression of Nef in endothelial cells synergized with K1 to facilitate vascular tube formation and cell proliferation, and enhance angiogenesis in a chicken CAM model.
Url:
DOI: 10.1093/nar/gku583
PubMed: 25104021
PubMed Central: 4150761
Affiliations:
- République populaire de Chine, États-Unis
- Californie, Pennsylvanie
- Los Angeles
- Université de Californie du Sud
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Le document en format XML
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</author>
<author><name sortKey="Zhu, Jianzhong" sort="Zhu, Jianzhong" uniqKey="Zhu J" first="Jianzhong" last="Zhu">Jianzhong Zhu</name>
<affiliation wicri:level="2"><nlm:aff id="AFF7">Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gao, Shou Jiang" sort="Gao, Shou Jiang" uniqKey="Gao S" first="Shou-Jiang" last="Gao">Shou-Jiang Gao</name>
<affiliation wicri:level="4"><nlm:aff id="AFF8">Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033</wicri:regionArea>
<placeName><region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author><name sortKey="Lu, Chun" sort="Lu, Chun" uniqKey="Lu C" first="Chun" last="Lu">Chun Lu</name>
<affiliation wicri:level="1"><nlm:aff id="AFF1">State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing</wicri:regionArea>
<wicri:noRegion>Nanjing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AFF2">Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, P.R. China</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing</wicri:regionArea>
<wicri:noRegion>Nanjing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AFF3">Department of Microbiology, Nanjing Medical University, Nanjing 210029, P.R. China</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Department of Microbiology, Nanjing Medical University, Nanjing 210029</wicri:regionArea>
<wicri:noRegion>Nanjing 210029</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nucleic Acids Research</title>
<idno type="ISSN">0305-1048</idno>
<idno type="eISSN">1362-4962</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Carcinogenesis (metabolism)</term>
<term>Cell Line</term>
<term>Cell Proliferation</term>
<term>Chick Embryo</term>
<term>Endothelial Cells (cytology)</term>
<term>Endothelial Cells (enzymology)</term>
<term>Endothelial Cells (metabolism)</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Nude</term>
<term>MicroRNAs (biosynthesis)</term>
<term>MicroRNAs (metabolism)</term>
<term>Neovascularization, Physiologic</term>
<term>PTEN Phosphohydrolase (metabolism)</term>
<term>Proto-Oncogene Proteins c-akt (metabolism)</term>
<term>Signal Transduction</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Viral Proteins (metabolism)</term>
<term>nef Gene Products, Human Immunodeficiency Virus (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Carcinogenèse (métabolisme)</term>
<term>Cellules endothéliales (cytologie)</term>
<term>Cellules endothéliales (enzymologie)</term>
<term>Cellules endothéliales (métabolisme)</term>
<term>Embryon de poulet</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Mâle</term>
<term>Néovascularisation physiologique</term>
<term>Phosphohydrolase PTEN (métabolisme)</term>
<term>Produits du gène nef du virus de l'immunodéficience humaine (métabolisme)</term>
<term>Prolifération cellulaire</term>
<term>Protéines proto-oncogènes c-akt (métabolisme)</term>
<term>Protéines virales (métabolisme)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris nude</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transduction du signal</term>
<term>microARN (biosynthèse)</term>
<term>microARN (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>MicroRNAs</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>microARN</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules endothéliales</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Cellules endothéliales</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Endothelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Carcinogenesis</term>
<term>Endothelial Cells</term>
<term>MicroRNAs</term>
<term>PTEN Phosphohydrolase</term>
<term>Proto-Oncogene Proteins c-akt</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Viral Proteins</term>
<term>nef Gene Products, Human Immunodeficiency Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinogenèse</term>
<term>Cellules endothéliales</term>
<term>Phosphohydrolase PTEN</term>
<term>Produits du gène nef du virus de l'immunodéficience humaine</term>
<term>Protéines proto-oncogènes c-akt</term>
<term>Protéines virales</term>
<term>Sérine-thréonine kinases TOR</term>
<term>microARN</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Cell Proliferation</term>
<term>Chick Embryo</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Nude</term>
<term>Neovascularization, Physiologic</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Embryon de poulet</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Mâle</term>
<term>Néovascularisation physiologique</term>
<term>Prolifération cellulaire</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Souris nude</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Kaposi's sarcoma (KS) is an AIDS-defining cancer with aberrant neovascularization caused by KS-associated herpesvirus (KSHV). Although the interaction between HIV-1 and KSHV plays a pivotal role in promoting the aggressive manifestations of KS, the pathogenesis underlying AIDS-KS remains largely unknown. Here we examined HIV-1 Nef protein promotion of KSHV oncoprotein K1-induced angiogenesis. We showed that both internalized and ectopic expression of Nef in endothelial cells synergized with K1 to facilitate vascular tube formation and cell proliferation, and enhance angiogenesis in a chicken CAM model. <italic>In vivo</italic>
experiments further indicated that Nef accelerated K1-induced angiogenesis and tumorigenesis in athymic nu/nu mice. Mechanistic studies revealed that Nef and K1 synergistically activated PI3K/AKT/mTOR signaling by downregulating PTEN. Furthermore, Nef and K1 induced cellular miR-718, which inhibited PTEN expression by directly targeting a seed sequence in the 3′ UTR of its mRNA. Inhibition of miR-718 expression increased PTEN synthesis and suppressed the synergistic effect of Nef- and K1-induced angiogenesis and tumorigenesis. These results indicate that, by targeting PTEN, miR-718 mediates Nef- and K1-induced angiogenesis via activation of AKT/mTOR signaling. Our results demonstrate an essential role of miR-718/AKT/mTOR axis in AIDS-KS and thus may represent an attractive therapeutic target.</p>
</div>
</front>
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<author><name sortKey="Stratakis, C A" uniqKey="Stratakis C">C.A. Stratakis</name>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Pennsylvanie</li>
</region>
<settlement><li>Los Angeles</li>
</settlement>
<orgName><li>Université de Californie du Sud</li>
</orgName>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Xue, Min" sort="Xue, Min" uniqKey="Xue M" first="Min" last="Xue">Min Xue</name>
</noRegion>
<name sortKey="Hao, Tingting" sort="Hao, Tingting" uniqKey="Hao T" first="Tingting" last="Hao">Tingting Hao</name>
<name sortKey="Hu, Minmin" sort="Hu, Minmin" uniqKey="Hu M" first="Minmin" last="Hu">Minmin Hu</name>
<name sortKey="Li, Wan" sort="Li, Wan" uniqKey="Li W" first="Wan" last="Li">Wan Li</name>
<name sortKey="Lu, Chun" sort="Lu, Chun" uniqKey="Lu C" first="Chun" last="Lu">Chun Lu</name>
<name sortKey="Lu, Chun" sort="Lu, Chun" uniqKey="Lu C" first="Chun" last="Lu">Chun Lu</name>
<name sortKey="Lu, Chun" sort="Lu, Chun" uniqKey="Lu C" first="Chun" last="Lu">Chun Lu</name>
<name sortKey="Lu, Hongmei" sort="Lu, Hongmei" uniqKey="Lu H" first="Hongmei" last="Lu">Hongmei Lu</name>
<name sortKey="Qin, Di" sort="Qin, Di" uniqKey="Qin D" first="Di" last="Qin">Di Qin</name>
<name sortKey="Xue, Min" sort="Xue, Min" uniqKey="Xue M" first="Min" last="Xue">Min Xue</name>
<name sortKey="Xue, Min" sort="Xue, Min" uniqKey="Xue M" first="Min" last="Xue">Min Xue</name>
<name sortKey="Xue, Min" sort="Xue, Min" uniqKey="Xue M" first="Min" last="Xue">Min Xue</name>
<name sortKey="Yan, Qin" sort="Yan, Qin" uniqKey="Yan Q" first="Qin" last="Yan">Qin Yan</name>
<name sortKey="Yao, Shuihong" sort="Yao, Shuihong" uniqKey="Yao S" first="Shuihong" last="Yao">Shuihong Yao</name>
<name sortKey="Zhou, Feng" sort="Zhou, Feng" uniqKey="Zhou F" first="Feng" last="Zhou">Feng Zhou</name>
<name sortKey="Zhu, Xiaofei" sort="Zhu, Xiaofei" uniqKey="Zhu X" first="Xiaofei" last="Zhu">Xiaofei Zhu</name>
</country>
<country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Zhu, Jianzhong" sort="Zhu, Jianzhong" uniqKey="Zhu J" first="Jianzhong" last="Zhu">Jianzhong Zhu</name>
</region>
<name sortKey="Gao, Shou Jiang" sort="Gao, Shou Jiang" uniqKey="Gao S" first="Shou-Jiang" last="Gao">Shou-Jiang Gao</name>
</country>
</tree>
</affiliations>
</record>
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