PEM is a cell cycle-specific antimetabolite drug which exerts antitumor effect mainly by interfering with the folic acid metabolic pathway during cell replication, and the results of RNA-seq showed that AKR1B10 knockdown exhibited the most significant effect on tumor cell cycle and DNA replication (Fig. 5A, Additional file 5: Fig. S2B); these suggested the potential mechanism that AKR1B10-increased lactate might promote chemoresistance in BM cells by regulating the cell cycle. This evidence concerns the gene MUC1 and neoplasm.