title: Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation and migration by upregulating DNMT1 via STAT3 activation.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS), the most common AIDS-related malignancy. KSHV vIL-6 promotes KS development, but the exact mechanisms remain unclear. Here, we reported that KSHV vIL-6 enhanced the expression of DNA methyltransferase 1 (DNMT1) in endothelial cells,increased the global genomic DNA methylation, and promoted cell proliferation and migration. And this effect could be blocked by the DNA methyltransferase inhibitor, 5-azadeoxycytidine. We also showed that vIL-6 induced up-regulation of DNMT1 was dependent on STAT3 activation. Therefore, the present study suggests that vIL-6 plays a role in KS tumorigenesis partly by activating DNMT1 and inducing aberrant DNA methylation, and it might be a potential target for KS therapy.
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Mo
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D044127:Epigenesis, Genetic; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014764:Viral Proteins; C120140:interleukin-6, RRV-HHV-8; D000077209:Decitabine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D001374:Azacitidine