In conjunction with the methionine adenosyltransferase 2A (MAT2A), MAT2B protein catalyses the formation of methyl donor S-adenosylmethionine to mediate cell metabolism, including proliferation and apoptosis. In this study, we investigated the functional and molecular mechanisms by which MAT2B influences triple-negative breast cancer (TNBC).

Our results demonstrated that targeting MAT2B could suppress cell growth and migration and induce apoptosis by inhibiting the AKT and ERK pathways in TNBC. Thus, targeting MAT2B requires further investigation as a therapeutic intervention for TNBC.

The mRNA level of MAT2B in three human TNBC cell lines and 40 TNBC tissue samples was analysed using quantitative reverse transcription polymerase chain reaction. The relationship between MAT2B expression and the clinicopathological characteristics of TNBC patients was also analysed. Further, MAT2B function was investigated using a series of in vitro and in vivo assays with cells in which MAT2B was inhibited using RNAi.

We found that the mRNA levels of MAT2B were upregulated in all human TNBC cell lines tested. Moreover, positive expression of MAT2B was significantly correlated with higher T classification and M-stage. We also found that a higher level of MAT2B was correlated with worse relapse-free survival (RFS) according to a log-rank test. Next, we showed that the direct inhibition, using RNAi, of MAT2B in MDA-MB-231 and MDA-MB-468 cells inhibited cell growth and migration and induced apoptosis. Knockdown of MAT2B in MDA-MB-231 cells also repressed the expression of phosphorylated AKT and phosphorylated extracellular regulated protein kinases 1/2 (ERK1/2). Both phosphorylated AKT and ERK1/2 inhibitors reduced cell growth and migration, and induced apoptosis in MDA-MB-231 cells. As expected, knockdown of MAT2B in MDA-MB-231 cells significantly decreased the rate of tumour growth in vivo.