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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | osteosarcoma | Research

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells

Authors: Qing He, Peng Hao, Gang He, Hantao Mai, Wenzhou Liu, Weiqiong Zhang, Kelin Zhang, Guifang Zhong, Ruilian Guo, Changzhi Yu, Yang Li, Chipiu Wong, Qian Chen, Yantao Chen

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3ʹ-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.
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Metadata
Title
IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells
Authors
Qing He
Peng Hao
Gang He
Hantao Mai
Wenzhou Liu
Weiqiong Zhang
Kelin Zhang
Guifang Zhong
Ruilian Guo
Changzhi Yu
Yang Li
Chipiu Wong
Qian Chen
Yantao Chen
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03549-7

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