Wu Jing, Xu Yuqiao, Mo Dongping, Huang Peijun, Sun Ruihong, Huang Lei, Pan Shiyang, Xu Jian
Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2014 Mar 27;9(3):e93478. doi: 10.1371/journal.pone.0093478. eCollection 2014.
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.
卡波西肉瘤相关疱疹病毒（KSHV）在病因上与卡波西肉瘤（KS）相关，卡波西肉瘤是最常见的与艾滋病相关的恶性肿瘤。KSHV病毒白细胞介素-6（vIL-6）促进KS的发展，但其确切机制仍不清楚。在此，我们报道KSHV vIL-6增强内皮细胞中DNA甲基转移酶1（DNMT1）的表达，增加全基因组DNA甲基化，并促进细胞增殖和迁移。这种效应可被DNA甲基转移酶抑制剂5-氮杂脱氧胞苷阻断。我们还表明，vIL-6诱导的DNMT1上调依赖于信号转导和转录激活因子3（STAT3）的激活。因此，本研究表明，vIL-6部分通过激活DNMT1和诱导异常DNA甲基化在KS肿瘤发生中起作用，它可能是KS治疗的潜在靶点。
