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Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression

Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐gen...

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Autores principales: Li, Huanhuan, Yang, Feng, Hu, Anpei, Wang, Xiaojing, Fang, Erhu, Chen, Yajun, Li, Dan, Song, Huajie, Wang, Jianqun, Guo, Yanhua, Liu, Yang, Li, Hongjun, Huang, Kai, Zheng, Liduan, Tong, Qiangsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895612/
https://www.ncbi.nlm.nih.gov/pubmed/31709724
http://dx.doi.org/10.15252/emmm.201910835
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author Li, Huanhuan
Yang, Feng
Hu, Anpei
Wang, Xiaojing
Fang, Erhu
Chen, Yajun
Li, Dan
Song, Huajie
Wang, Jianqun
Guo, Yanhua
Liu, Yang
Li, Hongjun
Huang, Kai
Zheng, Liduan
Tong, Qiangsong
author_facet Li, Huanhuan
Yang, Feng
Hu, Anpei
Wang, Xiaojing
Fang, Erhu
Chen, Yajun
Li, Dan
Song, Huajie
Wang, Jianqun
Guo, Yanhua
Liu, Yang
Li, Hongjun
Huang, Kai
Zheng, Liduan
Tong, Qiangsong
author_sort Li, Huanhuan
collection PubMed
description Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐generated circular RNA (circ‐CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose‐6‐phosphate isomerase, and phosphoglycerate kinase 1, while circ‐CUX1 binds to EWS RNA‐binding protein 1 (EWSR1) to facilitate its interaction with MYC‐associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ‐CUX1‐EWSR1 interaction or lentivirus mediating circ‐CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ‐CUX1 expression have lower survival probability. These results indicate circ‐CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression.
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spelling pubmed-68956122019-12-16 Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression Li, Huanhuan Yang, Feng Hu, Anpei Wang, Xiaojing Fang, Erhu Chen, Yajun Li, Dan Song, Huajie Wang, Jianqun Guo, Yanhua Liu, Yang Li, Hongjun Huang, Kai Zheng, Liduan Tong, Qiangsong EMBO Mol Med Articles Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT‐like homeobox 1 (CUX1) and CUX1‐generated circular RNA (circ‐CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose‐6‐phosphate isomerase, and phosphoglycerate kinase 1, while circ‐CUX1 binds to EWS RNA‐binding protein 1 (EWSR1) to facilitate its interaction with MYC‐associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ‐CUX1‐EWSR1 interaction or lentivirus mediating circ‐CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ‐CUX1 expression have lower survival probability. These results indicate circ‐CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression. John Wiley and Sons Inc. 2019-11-11 2019-12 /pmc/articles/PMC6895612/ /pubmed/31709724 http://dx.doi.org/10.15252/emmm.201910835 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Li, Huanhuan
Yang, Feng
Hu, Anpei
Wang, Xiaojing
Fang, Erhu
Chen, Yajun
Li, Dan
Song, Huajie
Wang, Jianqun
Guo, Yanhua
Liu, Yang
Li, Hongjun
Huang, Kai
Zheng, Liduan
Tong, Qiangsong
Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title_full Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title_fullStr Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title_full_unstemmed Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title_short Therapeutic targeting of circ‐CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression
title_sort therapeutic targeting of circ‐cux1/ewsr1/maz axis inhibits glycolysis and neuroblastoma progression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895612/
https://www.ncbi.nlm.nih.gov/pubmed/31709724
http://dx.doi.org/10.15252/emmm.201910835
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