Startseite JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells
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JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells

  • Xiaojun Xu ORCID logo EMAIL logo , Yongbin Ye , Xiaobo Wang , Bo Lu , Ziwen Guo und Shunjie Wu
Veröffentlicht/Copyright: 22. März 2020

Abstract

Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of multiple tumors including acute myeloid leukemia cells (AML). Our present study found that the expression of histone lysine demethylase Jumonji domain containing-3 (JMJD3) was increased in AML cells as compared with that in human primary bone marrow (HPBM) cells. Knockdown of JMJD3 can decrease the proliferation of AML cells and increase the chemosensitivity of daunorubicin (DNR) and cytarabine (Ara-C). By screening the expression of cytokines involved in AML progression, we found that knockdown of JMJD3 can inhibit the expression of interleukin-6 (IL-6). Recombinant IL-6 (rIL-6) can attenuate si-JMJD3-suppressed proliferation of AML cells. Mechanistically, JMJD3 can positively regulate the promoter activity and transcription of IL-6 mRNA, while had no effect on its mRNA stability. Further, JMJD3 can regulate the expression of p65, which can directly bind with promoter of IL-6 to increase its transcription. Over expression of p65 significantly attenuated si-JMJD3-suppressed expression of IL-6. Collectively, we revealed that JMJD3 can regulate the proliferation and chemosensitivity of AML cells via upregulation of IL-6. It suggested that JMJD3 might be a potential therapy target for AML treatment.


Corresponding author: Xiaojun Xu, Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen518107, China; and Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University, Zhongshan528403, China, E-mail:
Xiaojun Xu and Yongbin Ye contributed equally to this work.

Funding source: The Sanming Project of Medicine in Shenzhen

Award Identifier / Grant number: SZSM201911004

Funding source: The Science and Technology Research Major Project in Zhongshan

Award Identifier / Grant number: 2017B1002

Funding source: The Shenzhen Science and Technology Plan Basic Research Project

Award Identifier / Grant number: JCYJ20180307150408596

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The research was supported by the Sanming Project of Medicine in Shenzhen (No. SZSM201911004), the Science and Technology Research Major Project in Zhongshan (No. 2017B1002), and the Shenzhen Science and Technology Plan Basic Research Project (No. JCYJ20180307150408596).

  3. Conflict of interest statement: The authors declare no conflict of interest.

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Received: 2020-10-17
Accepted: 2021-03-11
Published Online: 2020-03-22
Published in Print: 2021-06-25

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