HMGB1 translocation is involved in the transformation of autophagy complexes and promotes chemoresistance in leukaemia

Kong,Qian; Xu,Lu-Hong; Xu,Wei; Fang,Jian-Pei; Xu,Hong-Gui

doi:10.3892/ijo.2015.2985

HMGB1 translocation is involved in the transformation of autophagy complexes and promotes chemoresistance in leukaemia

Authors:
- Qian Kong
- Lu-Hong Xu
- Wei Xu
- Jian-Pei Fang
- Hong-Gui Xu
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Affiliations: Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China, Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China
Published online on: May 4, 2015 https://doi.org/10.3892/ijo.2015.2985
Pages: 161-170

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Abstract

Acute lymphoblastic leukaemia (ALL) is a common paediatric cancer and is among the most curable cancers. However, the acquisition of drug resistance is a significant obstacle to the achievement of favourable outcomes, and autophagy is regarded as a mechanism that underlies chemoresistance. In this study, RT-qPCR was used to measure the expression of HMGB1 and Beclin1 in bone marrow mononuclear cells. A CCK-8 test was conducted to assess cell viability. Western blot, immunofluorescence and transmission electron microscopic analyses were performed to evaluate the autophagy levels. Immunoprecipitation analysis was performed to detect protein-protein interactions in the autophagy complexes. We found that HMGB1 expression correlated with the clinical status of ALL. In vitro, anticancer agent-induced cytotoxic effects were associated with autophagy-related drug resistance, and these effects were ameliorated by FIP200 depletion or the application of autophagy inhibitors. Moreover, the Ulk1‑Atg13-FIP200 complex, which promotes HMGB1 trafficking, acted upstream of the HMGB1-Beclin1 and PI3KC3-Beclin1 complexes and played a critical role in autophagy. Targeting the transformation of autophagic complexes or HMGB1 translocation may suppress autophagy and consequently overcome chemoresistance in leukaemia.

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