Fig. 6

FECR1 coordinately regulates DNMT1 and TET1. a Binding of FECR1 to the DNMT1 promoter. After RAT sequencing, the FECR1 binding sequences were blasted to the human genome at the UCSC website. Histone 3 lysine 27 (H3K27) acetylation signal was also shown correspondingly. b FECR1 downregulates DNMT1. Expression of DNMT1 was measured by qPCR. **p < 0.01 as compared with PBS and vector control groups. c FECR1 recruits TET1 enzyme. RNA-chromatin immunoprecipitation (RIP) was performed to identify FECR1-TET1 binding. The TET-FECR1 chromatin complex was immunoprecipitated with an antibody against TET1. After removal of crosslinking, the immunoprecipitated RNAs were reverse transcribed, and the TET-interacting FECR1 was measured by PCR. IgG was use as the antibody control, and cDNA was used as the positive control. d Putative model of FECR1 in breast cancer. In addition to the conventional FLI1 mRNA-oncoprotein model, FLI1 also produces circular RNA FECR1. Through the interaction with FLI1 promoter, FECR1 recruits TET1 demethylase and induces extensive DNA demethylation in the CpG islands. In addition, FECR1 also inhibits DNMT1, the critical enzyme that maintains DNA demethylation during DNA replication. Working together, FECR1 activates FLI1, which in turn promotes tumor cell invasion in breast cancers