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Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells |
| Authors: | Han, Nanumi Browse this author | | Anwar, Delnur Browse this author | | Hama, Naoki Browse this author | | Kobayashi, Takuto Browse this author | | Suzuki, Hidefumi Browse this author | | Takahashi, Hidehisa Browse this author | | Wada, Haruka Browse this author →KAKEN DB | | Otsuka, Ryo Browse this author | | Baghdadi, Muhammad Browse this author →KAKEN DB | | Seino, Ken-ichiro Browse this author →KAKEN DB |
| Keywords: | Bromodomain-containing protein 4 | | Interleukin-34 | | Cytokine induction | | Gene regulation | | JQ1 | | Tumor cell biology | | Tumor promotor |
| Issue Date: | 14-Oct-2020 |
| Publisher: | BioMed Central |
| Journal Title: | Inflammation and Regeneration |
| Volume: | 40 |
| Issue: | 1 |
| Start Page: | 25 |
| Publisher DOI: | 10.1186/s41232-020-00129-4 |
| Abstract: | Background: Interleukin (IL)-34 acts as an alternative ligand for the colony-stimulating factor-1 receptor and controls the biology of myeloid cells, including survival, proliferation, and differentiation. IL-34 has been reported to be expressed in cancer cells and to promote tumor progression and metastasis of certain cancers via the promotion of angiogenesis and immunosuppressive macrophage differentiation. We have shown in our previous reports that targeting IL-34 in chemo-resistant tumors in vitro resulted in a remarkable inhibition of tumor growth. Also, we reported poor prognosis in patients with IL-34-expressing tumor. Therefore, blocking of IL-34 is considered as a promising therapeutic strategy to suppress tumor progression. However, the molecular mechanisms that control IL-34 production are still largely unknown. Methods: IL-34 producing ovarian cancer cell line HM-1 was treated by bromodomain and extra terminal inhibitor JQ1. The mRNA and protein expression of IL-34 was evaluated after JQ1 treatment. Chromatin immunoprecipitation was performed to confirm the involvement of bromodomain-containing protein 4 (Brd4) in the regulation of theIl34gene. Anti-tumor effect of JQ1 was evaluated in mouse tumor model. Results: We identified Brd4 as one of the critical molecules that regulateIl34expression in cancer cells. Consistent with this, we found that JQ1 is capable of efficiently suppressing the recruitment of Brd4 to the promotor region ofIl34gene. Additionally, JQ1 treatment of mice bearing IL-34-producing tumor inhibited the tumor growth along with decreasingIl34expression in the tumor. Conclusion: The results unveiled for the first time the responsible molecule Brd4 that regulatesIl34expression in cancer cells and suggested its possibility as a treatment target. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/79754 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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