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

: Drug resistance severely reduces treatment efficiency of chemotherapy and leads to poor prognosis. However, regulatory factors of chemoresistant cancer cells are largely unknown. : The expression of estrogen receptor related receptors (ERRs) in chemoresistant cancer cells are checked. The roles of ERRγ in chemoresistance are confirmed by and studies. The mechanisms responsible for ERRγ-regulated expression of and are investigated. : 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 to increase its transcription. An elevated interaction between ERRγ and p65 in chemoresistant cells further strengthens transcription of . Further, ERRγ can increase the fatty acid oxidation (FAO) in chemoresistant cells via regulation of the rate-limiting enzyme of FAO. The upregulated ERRγ in chemoresistant cancer cells might be due to increased levels of N6-methyladenosine (mA) can trigger the splicing of precursor mRNA. : mA induced ERRγ confers chemoresistance of cancer cells through upregulation of and