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

Han, Nanumi; Anwar, Delnur; Hama, Naoki; Kobayashi, Takuto; Suzuki, Hidefumi; Takahashi, Hidehisa; Wada, Haruka; Otsuka, Ryo; Baghdadi, Muhammad; Seino, Ken-ichiro

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

Han, Nanumi; Anwar, Delnur; Hama, Naoki et al.

Inflammation and Regeneration, 2020, 40(1), 25

Permalink : https://hdl.handle.net/2115/79754

このアイテムのアクセス数:535件（2026-08-16 22:28 集計）

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https://doi.org/10.1186/s41232-020-00129-4			13

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アクセス権	open access
URI	https://hdl.handle.net/2115/79754
タイトル	Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells
著者	Han, Nanumi ; Anwar, Delnur ; Hama, Naoki ; Kobayashi, Takuto ; Suzuki, Hidefumi ; Takahashi, Hidehisa ; Wada, Haruka ; Otsuka, Ryo ; Baghdadi, Muhammad ; Seino, Ken-ichiro
著者名 Han, Nanumi
著者名 Anwar, Delnur
著者名 Hama, Naoki
著者名 Kobayashi, Takuto
著者名 Suzuki, Hidefumi
著者名 Takahashi, Hidehisa
e-Rad_Researcher 70392181 著者名 Wada, Haruka
著者名 Otsuka, Ryo
e-Rad_Researcher 60711570 著者名 Baghdadi, Muhammad
e-Rad_Researcher 20312845 著者名 Seino, Ken-ichiro
言語	英語
キーワード	Bromodomain-containing protein 4
	Interleukin-34
	Cytokine induction
	Gene regulation
	JQ1
	Tumor cell biology
	Tumor promotor
発行日	2020-10-14
出版者	BioMed Central
収録物名	Inflammation and Regeneration
巻(号)	40(1)
ページ	25
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/s41232-020-00129-4