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Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary Research

Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia

Authors: Fei-Fei Liu, Kai-Ling Wang, Li-Ping Deng, Xiao Liu, Min-yuan Wu, Tian-You Wang, Lei Cui, Zhi-Gang Li

Published in: Cancer Cell International | Issue 1/2018

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Abstract

Background

Low expression of E2F3a and caspase 8 associated protein 2 (CASP8AP2) are associated with poor prognosis of childhood acute lymphoblastic leukemia (ALL).

Methods

Dual-luciferase reporter assay and wild type as well as four mutated types of reporter plasmids were used to demonstrate the activation of E2F3a on CASP8AP2 transcription. The direct binding of E2F3a with the promoter of CASP8AP2 was shown by Chromatin Immunoprecipitation (ChIP). Cell proliferation activity and cell cycle were determined by MTS and flow cytometry in leukemic cells after treating with common chemotherapeutic drugs vincristine and daunorubicin.

Results

In this study, we found that up-regulation of E2F3a in leukemic cells led to increased fraction of cells in S and G2/M phase, accelerated proliferation, and enhanced sensitivity to vincristine and daunorubicin. ChIP and luciferase assay indicated that E2F3a could directly bind to two fragments in the wild type of CASP8AP2 promotor (− 206 to − 69 and − 677 to − 507), and activate its transcription activity which was reduced in mutated promotors. The effect of E2F3a on chemotherapeutic sensitivity of leukemic cells could be reversed by down-regulating CASP8AP2.

Conclusions

E2F3a could promote transcription and expression of CASP8AP2. The effect of E2F3a on chemotherapeutic sensitivity of ALL cells was implemented by regulating CASP8AP2 expression to a great extent.

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Metadata
Title
Transcription factor E2F3a regulates CASP8AP2 transcription and enhances sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia
Authors
Fei-Fei Liu
Kai-Ling Wang
Li-Ping Deng
Xiao Liu
Min-yuan Wu
Tian-You Wang
Lei Cui
Zhi-Gang Li
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0531-1

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