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The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA
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نویسنده
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li w. ,yan q. ,ding x. ,shen c. ,hu m. ,zhu y. ,qin d. ,lu h. ,krueger b.j. ,renne r. ,gao s.-j. ,lu c.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 4
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چکیده
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Kaposi’s sarcoma (ks)-associated herpesvirus (kshv) is a gammaherpesvirus etiologically associated with ks,a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells. kshv encodes 25 mature micrornas but their roles in kshv-induced tumor dissemination and angiogenesis remain unknown. here,we investigated kshv-encoded mir-k12-6-3p (mir-k6-3p) promotion of endothelial cell migration and angiogenesis,which are the underlying mechanisms of tumor dissemination and angiogenesis. we found that ectopic expression of mir-k6-3p promoted endothelial cell migration and angiogenesis. mass spectrometry,bioinformatics and luciferase reporter analyses revealed that mir-k6-3p directly targeted sequence in the 3’ untranslated region (utr) of sh3 domain binding glutamate-rich protein (sh3bgr). overexpression of sh3bgr reversed mir-k6-3p induction of cell migration and angiogenesis. mechanistically,mir-k6-3p downregulated sh3bgr,hence relieved stat3 from sh3bgr direct binding and inhibition,which was required for mir-k6-3p maximum activation of stat3 and induction of cell migration and angiogenesis. finally,deletion of mir-k6 from the kshv genome abrogated its effect on the sh3bgr/stat3 pathway,and kshv-induced migration and angiogenesis. our results illustrated that,by inhibiting sh3bgr,mir-k6-3p enhances cell migration and angiogenesis by activating the stat3 pathway,and thus contributes to the dissemination and angiogenesis of kshv-induced malignancies. © 2016 li et al.
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آدرس
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state key laboratory of reproductive medicine,nanjing medical university,nanjing,china,key laboratory of pathogen biology of jiangsu province,nanjing medical university,nanjing,china,department of microbiology,nanjing medical university,nanjing, China, department of microbiology,nanjing medical university,nanjing, China, department of microbiology,nanjing medical university,nanjing, China, department of microbiology,nanjing medical university,nanjing, China, department of microbiology,nanjing medical university,nanjing, China, department of molecular microbiology and immunology,keck school of medicine,university of southern california,los angeles,ca, United States, department of microbiology,nanjing medical university,nanjing, China, department of obstetrics,the first affiliated hospital of nanjing medical university,nanjing, China, department of molecular genetics and microbiology,university of florida,gainesville,fl, United States, department of molecular genetics and microbiology,university of florida,gainesville,fl, United States, department of molecular microbiology and immunology,keck school of medicine,university of southern california,los angeles,ca, United States, state key laboratory of reproductive medicine,nanjing medical university,nanjing,china,key laboratory of pathogen biology of jiangsu province,nanjing medical university,nanjing,china,department of microbiology,nanjing medical university,nanjing, China
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Authors
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