N6-methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming

Year: 2020

Type: article

Abstract: Background: Drug resistance severely reduces treatment efficiency of chemotherapy and leads to poor prognosis. However, regulatory factors of chemoresistant cancer cells are largely unknown. Methods: The expression of estrogen receptor related receptors (ERRs) in chemoresistant cancer cells are checked. The roles of ERRγ in chemoresistance are confirmed by in vitro and in vivo studies. The mechanisms responsible for ERRγ-regulated expression of ABCB1 and CPT1B are investigated. Results: The expression of ERRγ is upregulated in chemoresistant cancer cells. Targeted inhibition of ERRγ restores the chemosensitivity. ERRγ can directly bind to the promoter of ABCB1 to increase its transcription. An elevated interaction between ERRγ and p65 in chemoresistant cells further strengthens transcription of ABCB1. Further, ERRγ can increase the fatty acid oxidation (FAO) in chemoresistant cells via regulation of CPT1B, the rate-limiting enzyme of FAO. The upregulated ERRγ in chemoresistant cancer cells might be due to increased levels of N6-methyladenosine (m(6)A) can trigger the splicing of precursor ESRRG mRNA. Conclusions: m(6)A induced ERRγ confers chemoresistance of cancer cells through upregulation of ABCB1 and CPT1B.

Source: Theranostics

DOI: 10.7150/thno.40144

Authors: Zhuojia Chen, Long Wu, Jiawang Zhou, Xinyao Lin, Yanxi Peng, Lichen Ge, Cheng-Ming Chiang, Hui Huang, Hongsheng Wang, Weiling He

Institutions: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, University of Maryland, Baltimore, Sun Yat-sen University, Nanjing General Hospital of Nanjing Military Command, Nanjing University, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Eighth Affiliated Hospital of Sun Yat-sen University, The First Affiliated Hospital, Sun Yat-sen University

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,671

Funders: Cancer Prevention and Research Institute of Texas, National Natural Science Foundation of China, Sun Yat-sen University, Natural Science Foundation of Guangdong Province, Guangdong Provincial Key Laboratory of Construction Foundation, National Institutes of Health, Fundamental Research Funds for the Central Universities, National Cancer Institute

OpenAlex ID: W3005729925