METTL3/IGF2BP1 promotes the development of triple-negative breast cancer by mediating m6A methylation modification of PRMT7.

BACKGROUND

PRMT7 is upregulated in breast cancer and promotes tumor metastasis. Here we aimed to explore the function and mechanism of PRMT7 in triple-negative breast cancer (TNBC).

METHODS

The expression of PRMT7, METTL3 and IGF2BP1 was detected by immunohistochemistry (IHC), qRT-PCR and western blot. Cell viability and proliferation were measured using MTT and EdU assay. Flow cytometry and TUNEL assays were used to evaluate apoptosis. Invasion and migration were assessed by transwell and wound healing assays, respectively. Glucose consumption and lactate production were measured to assess glycolysis. In addition, the interaction between METTL3 and PRMT was verified by methylated RNA immunoprecipitation. The roles of METTL3 and PRMT in vivo were investigated through a xenograft model.

RESULTS

PRMT7 was upregulated in TNBC tissues and cells, and the knockdown of PRMT7 inhibited cell proliferation, invasion, migration and glycolysis, but induced apoptosis in TNBC cells. METTL3/IGF2BP1 enhanced PRMT7 expression by mediating the m6A methylation modification of PRMT7. Besides, METTL3 knockdown suppressed the progression of TNBC cells and regulated the WNT/β-catenin pathway via PRMT7. Moreover, silencing METTL3 restrained TNBC tumor growth in vivo through regulating PRMT7.

CONCLUSION

METTL3/IGF2BP1 facilitates the progression of TNBC by mediating m6A methylation modification of PRMT7.