The mechanism of cancer induction involves an aberrant expression of oncogenes whose functions can be controlled by RNAi with miRNA. Even foreign bacterial RNA may interfere with the expression of oncogenes. Here we show that bacterial plasmid mucAB and its Escherichia coli genomic homolog umuDC, carrying homologies that match the mouse anti-miR-145, sequestered the miR-145 function in mouse BALB 3T3 cells in a tetracycline (Tet)-inducible manner, activated oncogene Nedd9 and its downstream Aurkb, and further enhanced microcolony formation and cellular transformation as well as the short fragments of the bacterial gene containing the anti-miR-145 sequence. Furthermore, mucAB transgenic mice showed a 1.7-fold elevated tumor incidence compared with wild-type mice after treatments with 3-methylcolanthrene. However, the mutation frequency in intestinal stem cells of the mucAB transgenic mice was unchanged after treatment with X-rays or ethyl-nitrosourea, indicating that the target of mucAB/umuDC is the promotion stage in carcinogenesis. Implications: Foreign bacterial genes can exert oncogenic activity via RNAi, if endogenously expressed. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/18/9/1271/F1.large.jpg. Visual Overview

中文翻译：

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细菌 SOS 基因 mucAB/umuDC 通过 miR-145 海绵激活癌基因 Nedd9/Aurkb 促进小鼠肿瘤


癌症诱导机制涉及癌基因的异常表达，其功能可以通过 RNAi 和 miRNA 来控制。即使是外来细菌 RNA 也可能干扰癌基因的表达。在这里，我们发现细菌质粒 mucAB 及其大肠杆菌基因组同源物 umuDC 携带与小鼠抗 miR-145 相匹配的同源性，以四环素 (Tet) 诱导的方式隔离小鼠 BALB 3T3 细胞中的 miR-145 功能，激活癌基因Nedd9及其下游Aurkb，进一步增强了微菌落形成和细胞转化以及含有抗miR-145序列的细菌基因的短片段。此外，与野生型小鼠相比，用 3-甲基colanthrene 治疗后，mucAB 转基因小鼠的肿瘤发病率增加了 1.7 倍。然而，mucAB转基因小鼠的肠道干细胞在X射线或乙基亚硝基脲处理后突变频率没有变化，表明mucAB/umuDC的靶点是癌变的促进阶段。意义：如果内源表达，外源细菌基因可以通过 RNAi 发挥致癌活性。视觉概述：http://mcr.aacrjournals.org/content/molcanres/18/9/1271/F1.large.jpg。视觉概览