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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2020

Open Access 01-12-2020 | Neuroblastoma | Research

RETRACTED ARTICLE: HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression

Authors: Huajie Song, Dan Li, Xiaojing Wang, Erhu Fang, Feng Yang, Anpei Hu, Jianqun Wang, Yanhua Guo, Yang Liu, Hongjun Li, Yajun Chen, Kai Huang, Liduan Zheng, Qiangsong Tong

Published in: Journal of Hematology & Oncology | Issue 1/2020

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Abstract

Background

Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of glycolytic genes in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain elusive.

Methods

Crucial transcriptional regulators and their downstream glycolytic genes were identified by integrative analysis of a publicly available expression profiling dataset. In vitro and in vivo assays were undertaken to explore the biological effects and underlying mechanisms of transcriptional regulators in NB cells. Survival analysis was performed by using Kaplan-Meier method and log-rank test.

Results

Hepatocyte nuclear factor 4 alpha (HNF4A) and its derived long noncoding RNA (HNF4A-AS1) promoted aerobic glycolysis and NB progression. Gain- and loss-of-function studies indicated that HNF4A and HNF4A-AS1 facilitated the glycolysis process, glucose uptake, lactate production, and ATP levels of NB cells. Mechanistically, transcription factor HNF4A increased the expression of hexokinase 2 (HK2) and solute carrier family 2 member 1 (SLC2A1), while HNF4A-AS1 bound to heterogeneous nuclear ribonucleoprotein U (hnRNPU) to facilitate its interaction with CCCTC-binding factor (CTCF), resulting in transactivation of CTCF and transcriptional alteration of HNF4A and other genes associated with tumor progression. Administration of a small peptide blocking HNF4A-AS1-hnRNPU interaction or lentivirus-mediated short hairpin RNA targeting HNF4A-AS1 significantly suppressed aerobic glycolysis, tumorigenesis, and aggressiveness of NB cells. In clinical NB cases, high expression of HNF4A-AS1, hnRNPU, CTCF, or HNF4A was associated with poor survival of patients.

Conclusions

These findings suggest that therapeutic targeting of HNF4A-AS1/hnRNPU/CTCF axis inhibits aerobic glycolysis and NB progression.
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Metadata
Title
RETRACTED ARTICLE: HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression
Authors
Huajie Song
Dan Li
Xiaojing Wang
Erhu Fang
Feng Yang
Anpei Hu
Jianqun Wang
Yanhua Guo
Yang Liu
Hongjun Li
Yajun Chen
Kai Huang
Liduan Zheng
Qiangsong Tong
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00857-7

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