The effect of METTL3 RNA methyltransferase inhibition on breast cancer cell gene expression

MCF-7 and MDA-MB-231 cells were treated with the STM2457 METTL3 RNA methyltransferase inhibitor. The effect on global gene expression and alternative splicing was determined. Overall design: MCF-7 were maintained in phenol-red free RPMI-1640 medium supplemented with 100 µg/mL penicillin, 100 µg/mL streptomycin, 1 mM sodium pyruvate, and 10% charcoal “depleted” FBS. MCF-7 cells were either treated with vehicle (DMSO) or estradiol (10nM), alone or in combination with the STM2457 (10µM) METTL3 inhibitor. MDA-MB-231 cells were maintained in in RPMI-1640 medium supplemented with 100 µg/mL penicillin, 100 µg/mL streptomycin, 1 mM sodium pyruvate and 10% fetal bovine serum (FBS). MDA-MB-231 cells were treated with either vehicle (DMSO) or STM2457 (10µM). Cells were treated twice over 6 days (day 0 and day 3) and RNA harvested on day 6. The effect on global gene expression and alternative splicing was determined by RNA sequencing.