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Molecular Cancer Research
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Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge

Hiroshi Tanooka, Ayako Inoue, Ryou-u Takahashi, Kouichi Tatsumi, Kazuo Fujikawa, Tetsuji Nagao, Masamichi Ishiai, Fumiko Chiwaki, Kazuhiko Aoyagi, Hiroki Sasaki and Takahiro Ochiya
Hiroshi Tanooka
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
2Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan.
3Biological Effects Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
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  • For correspondence: tanooka-h@wind.ocn.ne.jp
Ayako Inoue
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
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Ryou-u Takahashi
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
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  • ORCID record for Ryou-u Takahashi
Kouichi Tatsumi
3Biological Effects Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan.
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Kazuo Fujikawa
4Department of Life Science, Faculty of Science and Technology, Kindai University, Higashiosaka, Japan.
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Tetsuji Nagao
4Department of Life Science, Faculty of Science and Technology, Kindai University, Higashiosaka, Japan.
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Masamichi Ishiai
2Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan.
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Fumiko Chiwaki
5Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan.
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Kazuhiko Aoyagi
5Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan.
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Hiroki Sasaki
5Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan.
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Takahiro Ochiya
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
6Department of Molecular and Cellular Medicine, Tokyo Medical University, Tokyo, Japan.
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DOI: 10.1158/1541-7786.MCR-20-0137 Published September 2020
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Abstract

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.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Mol Cancer Res 2020;18:1271–7

  • Received February 10, 2020.
  • Revision received March 31, 2020.
  • Accepted June 2, 2020.
  • Published first June 8, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Research: 18 (9)
September 2020
Volume 18, Issue 9
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Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge
Hiroshi Tanooka, Ayako Inoue, Ryou-u Takahashi, Kouichi Tatsumi, Kazuo Fujikawa, Tetsuji Nagao, Masamichi Ishiai, Fumiko Chiwaki, Kazuhiko Aoyagi, Hiroki Sasaki and Takahiro Ochiya
Mol Cancer Res September 1 2020 (18) (9) 1271-1277; DOI: 10.1158/1541-7786.MCR-20-0137

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Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge
Hiroshi Tanooka, Ayako Inoue, Ryou-u Takahashi, Kouichi Tatsumi, Kazuo Fujikawa, Tetsuji Nagao, Masamichi Ishiai, Fumiko Chiwaki, Kazuhiko Aoyagi, Hiroki Sasaki and Takahiro Ochiya
Mol Cancer Res September 1 2020 (18) (9) 1271-1277; DOI: 10.1158/1541-7786.MCR-20-0137
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