Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation.
Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation.
复制标题
DOI：
10.1002/path.2962
复制
发表时间：
2011-11
影响因子：
7.3
通讯作者：
Zheng, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Kang, Jeong-Gu;Majerciak, Vladimir;Uldrick, Thomas S.;Wang, Xiaohong;Kruhlak, Michael;Yarchoan, Robert;Zheng, Zhi-Ming
关键词：
卡波济肉瘤相关疱疹病毒（Kaposi sarcoma-associated herpesvirus，KSHV）编码一种病毒性白细胞介素6（viral interleukin 6，vIL 6），其模拟人IL 6（human IL 6，hIL 6）的许多活性。vIL 6和hIL 6在刺激KSHV引起的肿瘤增殖中起重要作用。在这里，我们提供的证据表明，一个miRNA途径参与调节vIL 6和hIL 6的表达，通过其开放阅读框架（ORF）中的结合位点。我们显示hsa-miR-1293对vIL 6的直接抑制和hsa-miR-608对hIL 6的直接抑制。通过引入点突变破坏vIL 6 miR-1293种子匹配，逆转miR-1293对vIL 6的抑制。此外，转染相应的miRNA抑制剂可以增强KSHV感染细胞中vIL 6或hIL 6的表达。人淋巴结切片的原位杂交显示，miR-1293主要在生发中心表达，但在淋巴结的外套带中缺乏，其中vIL 6的表达通常在患有KSHV相关的多中心Castleman病的患者中发现，这提供了解剖学相关性的证据。总之，我们的研究表明，IL 6的表达可以通过其ORF中的miRNA相互作用来调节，并为这些相互作用在KSHV相关疾病的发病机制中的作用提供了证据。
Kaposi sarcoma-associated herpesvirus (KSHV) encodes a viral interleukin 6 (vIL6) that mimics many activities of human IL6 (hIL6). Both vIL6 and hIL6 play important roles in stimulating the proliferation of tumors caused by KSHV. Here, we provide evidence that a miRNA pathway is involved in regulation of vIL6 and hIL6 expression through binding sites in their open reading frames (ORF). We show a direct repression of vIL6 by hsa-miR-1293 and hIL6 by hsa-miR-608. The repression of vIL6 by miR-1293 was reversed by disruption of the vIL6 miR-1293 seed match through the introduction of point mutations. In addition, expression of vIL6 or hIL6 in KSHV-infected cells could be enhanced by transfection of the respective miRNA inhibitors. In situ hybridization of human lymph node sections revealed that miR-1293 is primarily expressed in the germinal center, but is deficient in the mantle zone of lymph nodes where the expression of vIL6 is often found in patients with KSHV-associated multicentric Castleman’s disease, providing evidence of an anatomic correlation. Together, our study indicates that IL6 expression can be regulated by miRNA interactions in its ORF and provides evidence for the role of these interactions in the pathogenesis of KSHV-associated diseases.
登录
查看更多内容
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
56.9
作者：
Chatterjee, M;Osborne, J;Moore, PS
通讯作者：
Moore, PS
影响因子：
3.7
作者：
Katano, H;Sato, Y;Sata, T
通讯作者：
Sata, T
影响因子：
20.3
作者：
Aoki, Y;Yarchoan, R;Tosato, G
通讯作者：
Tosato, G
DOI：
10.1073/pnas.0500613102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Eis, PS;Tam, W;Dahlberg, JE
通讯作者：
Dahlberg, JE