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A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling
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نویسنده
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hu m. ,wang c. ,li w. ,lu w. ,bai z. ,qin d. ,yan q. ,zhu j. ,krueger b.j. ,renne r. ,gao s.-j. ,lu c.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 9
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چکیده
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Kaposi's sarcoma (ks) is a highly disseminated angiogenic tumor of endothelial cells linked to infection by kaposi's sarcoma-associated herpesvirus (kshv). kshv encodes more than two dozens of mirnas but their roles in kshv-induced tumor dissemination and metastasis remain unknown. here,we found that ectopic expression of mir-k12-3 (mir-k3) promoted endothelial cell migration and invasion. bioinformatics and luciferase reporter analyses showed that mir-k3 directly targeted g protein-coupled receptor (gpcr) kinase 2 (grk2,official gene symbol adrbk1). importantly,overexpression of grk2 reversed mir-k3 induction of cell migration and invasion. furthermore,the chemokine receptor cxcr2,which was negatively regulated by grk2,was upregulated in mir-k3-transduced endothelial cells. knock down of cxcr2 abolished mir-k3-induced cell migration and invasion. moreover,mir-k3 downregulation of grk2 relieved its direct inhibitory effect on akt. both cxcr2 induction and the release of akt from grk2 were required for mir-k3 maximum activation of akt and induction of cell migration and invasion. finally,deletion of mir-k3 from the kshv genome abrogated its effect on the grk2/cxcr2/akt pathway and kshv-induced migration and invasion. our data provide the first-line evidence that,by repressing grk2,mir-k3 facilitates cell migration and invasion via activation of cxcr2/akt signaling,which likely contribute to the dissemination of kshv-induced tumors. © 2015 hu 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 pathology,the first affiliated hospital of nanjing medical university,nanjing, China, department of microbiology,nanjing medical university,nanjing, China, department of endocrinology and metabolism,huai’an first people’s hospital,nanjing medical university,6 beijing road west,huai’an,jiangsu, 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, cancer virology program,university of pittsburgh cancer institute,pittsburgh,pa, United States, 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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