KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming
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DOI：
10.1101/gad.553410
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发表时间：
2010-01-15
影响因子：
10.5
通讯作者：
Boshoff, Chris
中科院分区：
文献类型：
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作者：
Hansen, Amy;Henderson, Stephen;Boshoff, Chris
卡波西肉瘤疱疹病毒 (KSHV) 诱导内皮细胞转录重编程。特别是，KSHV 感染的淋巴内皮细胞 (LEC) 显示与血管内皮细胞 (BEC) 相关的基因上调。因此，卡波西肉瘤中感染 KSHV 的肿瘤细胞是低分化内皮细胞，表达 LEC 和 BEC 标记物。 MicroRNA (miRNA) 是短的非编码 RNA 分子，可在转录后负向调节基因表达。在这里，我们验证了 KSHV 编码的 miRNA 在卡波西肉瘤病变中的表达，并证明这些 miRNA 通过沉默细胞转录因子 MAF（肌肉腱膜纤维肉瘤癌基因同源物）来促进病毒诱导的重编程。 MAF 在 LEC 中表达，但在 BEC 中不表达。我们确定了 MAF 作为转录抑制因子的新作用，阻止 BEC 特异性基因的表达，从而维持 LEC 的分化状态。这些发现表明，病毒 miRNA 可以影响受感染细胞的分化状态，从而有助于 KSHV 诱导的肿瘤发生。
Kaposi sarcoma herpesvirus (KSHV) induces transcriptional reprogramming of endothelial cells. In particular, KSHV-infected lymphatic endothelial cells (LECs) show an up-regulation of genes associated with blood vessel endothelial cells (BECs). Consequently, KSHV-infected tumor cells in Kaposi sarcoma are poorly differentiated endothelial cells, expressing markers of both LECs and BECs. MicroRNAs (miRNAs) are short noncoding RNA molecules that act post-transcriptionally to negatively regulate gene expression. Here we validate expression of the KSHV-encoded miRNAs in Kaposi sarcoma lesions and demonstrate that these miRNAs contribute to viral-induced reprogramming by silencing the cellular transcription factor MAF (musculoaponeurotic fibrosarcoma oncogene homolog). MAF is expressed in LECs but not in BECs. We identify a novel role for MAF as a transcriptional repressor, preventing expression of BEC-specific genes, thereby maintaining the differentiation status of LECs. These findings demonstrate that viral miRNAs could influence the differentiation status of infected cells, and thereby contribute to KSHV-induced oncogenesis.