Histone deacetylase inhibitor chidamide regulates the Wnt/beta-catenin pathway by MYCN/DKK3 in B-ALL

Zhao, Linlin1; Lv, Chengfang2; Sun, Lili3; Li, Qi3; Wang, Yuhuang3; Wu, Min3; Wang, Yuying3; Guo, Zhibo3; Bian, Sicheng3; Kong, Desheng4; Lin, Leilei3; Wang, Yu3; Zhou, Jin2; Li, Yinghua3

2021-02-01

10.1007/s10637-021-01079-5

INVESTIGATIONAL NEW DRUGS   影响因子和分区

0167-6997

1573-0646

Our previous studies revealed that MYCN downregulates the expression of DKK3, activates the Wnt/beta-catenin signalling pathway at the transcriptional level, and thereby promotes the development of B cell acute lymphocytic leukaemia (B-ALL) but does not affect the methylation of the DKK3 promoter. Some studies have shown that MYCN is associated with histone acetylation. We speculate that histone deacetylase inhibitors (HDACis) can inhibit the Wnt/beta-catenin signalling pathway by inhibiting MYCN and increasing the expression of DKK3. Based on previous experiments, we tested this hypothesis by analysing the changes in MYCN, DKK3 and the Wnt/beta-catenin signalling pathways in B-ALL cells after treatment with the selective HDACi chidamide. The in vitro and in vivo experiments confirmed that chidamide inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of histone deacetylase, and these effects resulted in inhibition of the Wnt/beta-catenin signalling pathway and the proliferation of B-ALL cells. These findings indicate that chidamide might be used alone or in combination with other chemotherapy regimens for patients with B-ALL and thus provide a new approach to the treatment of B-ALL.

B cell acute lymphocytic leukaemia Chidamide MYCN DKK3 Wnt/beta-catenin

SCI

英语

通讯

Scientific Research and Innovation Fund of the First affiliated Hospital of Harbin Medical University[2020B15] ; Foundation for the Dean of Southern University of Science and Technology Hospital[2020-A3]

Oncology ; Pharmacology & Pharmacy

Oncology ; Pharmacology & Pharmacy

WOS:000616902700001

SPRINGER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Harbin Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Harbin, Peoples R China
2.Southern Univ Sci & Technol Hosp, Dept Hematol, Shenzhen, Peoples R China
3.Harbin Med Univ, Affiliated Hosp 1, Dept Hematol, Harbin, Peoples R China
4.Harbin Med Univ, Affiliated Hosp 4, Dept Hematol, Harbin, Peoples R China

Zhao, Linlin,Lv, Chengfang,Sun, Lili,et al. Histone deacetylase inhibitor chidamide regulates the Wnt/beta-catenin pathway by MYCN/DKK3 in B-ALL[J]. INVESTIGATIONAL NEW DRUGS,2021.

Zhao, Linlin.,Lv, Chengfang.,Sun, Lili.,Li, Qi.,Wang, Yuhuang.,...&Li, Yinghua.(2021).Histone deacetylase inhibitor chidamide regulates the Wnt/beta-catenin pathway by MYCN/DKK3 in B-ALL.INVESTIGATIONAL NEW DRUGS.

Zhao, Linlin,et al."Histone deacetylase inhibitor chidamide regulates the Wnt/beta-catenin pathway by MYCN/DKK3 in B-ALL".INVESTIGATIONAL NEW DRUGS (2021).