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Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells

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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
Cytokine induction
Gene regulation
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.
Type: article
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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