Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded microRNAs promote matrix metalloproteinases (MMPs) expression and pro-angiogenic cytokine secretion in endothelial cells.
The human oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to Kaposi's sarcoma (KS), a tumor of endothelial cells characterized by angiogenesis and invasiveness. KSHV genome encodes 25 mature microRNAs (miRNAs), but their roles in KSHV-induced tumor dissemination and angiogenesis are not fully understood. In this study, we constructed the sensor reporters of KSHV miRNAs and used a luciferase reporter assay to demonstrate the function of the mimics of KSHV miRNAs. Then, we examined the expression of matrix metalloproteinases (MMPs) and pro-angiogenic cytokines that are related to cell migration and angiogenesis in the KSHV 25 miRNAs transfected endothelial cells. We found that all KSHV miRNAs increased the expression of the transcripts of MMP1, MMP13, VEGFA, and VEGFR2 in different degrees, as well as the secretion of VEGFA protein in the supernatant of endothelial cells. Our results reveal that KSHV miRNAs contribute to regulating MMPs and expression of pro-angiogenic factors, thus, suggesting that these miRNAs might play a crucial role in KSHV-induced cell motility and angiogenesis.
The College of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, P. R. China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, P. R. China.|Department of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Yuanyuan
Y
Guo
Department of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Wan
W
Li
Department of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Jie
J
Qin
Department of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Chun
C
Lu
Department of Hematology and Oncology, Jiangsu Province Geriatric Hospital, Nanjing, P. R. China.
Weifei
0000-0003-1876-9064
W
Fan
D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000821:virology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic; D012367:RNA, Viral / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000503:physiopathology / Q000821:virology*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D035683:MicroRNAs; D012367:RNA, Viral; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008156:Luciferases; D020782:Matrix Metalloproteinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
KSHV miRNAs; MMPs; pro-angiogenic cytokines