Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Cell Rep. 2019 Dec 3;29(10):2961-2969.e6. doi: 10.1016/j.celrep.2019.11.005.
Many tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi's sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells confers a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of miR-15/16 family miRNAs. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is an unusual example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor-suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.
许多肿瘤病毒编码源自细胞的致癌基因。在这里，我们报告了一种细胞肿瘤抑制因子的致癌病毒模拟物。卡波济肉瘤相关疱疹病毒 (KSHV) microRNA (miRNA) miR-K6-5p 与肿瘤抑制性细胞 miR-15/16 miRNA 家族具有序列相似性。我们表明，miR-K6-5p 抑制细胞周期进程，这是 miR-16 的标志功能。miR-K6-5p 调节保守的 miR-15/16 家族 miRNA 靶标，包括许多细胞周期调节剂。在 KSHV 转化的 B 细胞中抑制 miR-K6-5p 赋予显著的生长优势。总之，我们的数据表明 KSHV 编码了 miR-15/16 家族 miRNA 的功能性模拟物。虽然已经非常清楚，致癌病毒编码源自细胞的致癌基因，但这是一个罕见的例子，即致癌病毒编码了细胞肿瘤抑制因子的病毒模拟物。编码肿瘤抑制性 miRNA 可以帮助 KSHV 平衡病毒致癌基因的表达，从而避免在健康宿主中发生严重的发病机制。
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