众所周知，小鼠乳腺肿瘤病毒（MMTV）是导致小鼠乳腺癌的原因。此前，我们已经证明 MMTV 会失调 MMTV 感染的乳腺和 MMTV 诱导的肿瘤中宿主 miR-17-92 簇的表达。这个簇，更广为人知的名字是 oncomiR-1，在癌症，尤其是乳腺癌中经常失调。在这项研究中，我们的目标是揭示 MMTV 和集群之间的功能交互。我们的结果表明，MMTV 表达导致乳腺上皮 HC11 和 HEK293T 细胞中簇的失调，其中 miR-92a 簇成员的表达受影响最大。相反，整个或部分簇的过度表达显着抑制 MMTV 表达。值得注意的是，单独簇成员 miR-92a 的过表达抑制 MMTV 表达的程度与完整/部分簇的过表达相同。抑制 miR-92a 导致 MMTV 表达几乎完全恢复，而删除/替换 miR-92a 种子序列则挽救了 MMTV 表达。双荧光素酶测定确定 MMTV 基因组 RNA 是 miR-92a 的潜在靶标。这些结果表明，miR-17-92 簇是细胞众所周知的基于 miRNA 的抗病毒反应的一部分，可阻止传入的 MMTV 感染。因此，这项研究提供了第一个证据，强调了宿主 miRNA 在调节 MMTV 复制和潜在影响肿瘤发生方面的生物学意义。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The mouse mammary tumor virus (MMTV) is a well-known cause of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell's well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.