RT Journal Article
SR Electronic
T1 Bacterial SOS Genes <em>mucAB/umuDC</em> Promote Mouse Tumors by Activating Oncogenes <em>Nedd9/Aurkb</em> via a miR-145 Sponge
JF Molecular Cancer Research
JO Mol Cancer Res
FD American Association for Cancer Research
SP 1271
OP 1277
DO 10.1158/1541-7786.MCR-20-0137
VO 18
IS 9
A1 Tanooka, Hiroshi
A1 Inoue, Ayako
A1 Takahashi, Ryou-u
A1 Tatsumi, Kouichi
A1 Fujikawa, Kazuo
A1 Nagao, Tetsuji
A1 Ishiai, Masamichi
A1 Chiwaki, Fumiko
A1 Aoyagi, Kazuhiko
A1 Sasaki, Hiroki
A1 Ochiya, Takahiro
YR 2020
UL http://mcr.aacrjournals.org/content/18/9/1271.abstract
AB 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.