Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge
Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge
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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
DOI：
10.1158/1541-7786.mcr-20-0137
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ochiya T.
中科院分区：
文献类型：
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作者：
Tanooka H;Inoue A;Takahashi RU;Tatsumi K;Fujikawa K;Nagao T;Ishiai M;Chiwaki F;Aoyagi K;Sasaki H;Ochiya T.
癌症诱导的机制涉及癌基因的异常表达，其功能可以通过使用miRNA的RNAi来控制。甚至外来细菌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mucDC，携带与小鼠anti-miR-145匹配的同源物，以四环素（泰特）诱导的方式在小鼠BALB 3 T3细胞中隔离miR-145功能，激活癌基因Nedd 9及其下游Aurkb，并进一步增强了小菌落形成和细胞转化，以及含有抗miR-16的细菌基因的短片段，145序列。此外，mucAB转基因小鼠与野生型小鼠相比，用3-甲基colanthrene治疗后，肿瘤发病率升高了1.7倍。然而，经X射线或乙基亚硝基脲处理后，mucAB转基因小鼠肠干细胞中的突变频率没有变化，表明mucAB/umuDC的靶点是致癌过程中的促进阶段。mcr.aacrjournals.org/content/molcanres/18/9/1271/F1.large.jpg
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 plasmidmucABand itsEscherichia coligenomic homologumuDC,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 oncogeneNedd9and its downstreamAurkb,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,mucABtransgenic 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 themucABtransgenic mice was unchanged after treatment with X-rays or ethyl-nitrosourea, indicating that the target ofmucAB/umuDCis the promotion stage in carcinogenesis.ImplicationsForeign bacterial genes can exert oncogenic activity via RNAi, if endogenously expressed.Visual Overviewhttp://mcr.aacrjournals.org/content/molcanres/18/9/1271/F1.large.jpg.