Lidamycin regulates p53 expression by repressing Oct4 transcription

•We found that lidamycin (LDM) up-regulates tumor suppressor gene p53 expression by repressing Oct4 transcription.•Suppression of Oct4 expression leads to activation of p53 by low-dose LDM.•Knockdown Oct4 by siRNA results in p53 activation.•Ectopical expression of Oct4 blocks p53 activation by low-dose LDM.•Oct4 is downregulated by low-dose LDM through LDP directly binding to Oct4 promoter. Antitumor antibiotic lidamycin (LDM) is widely used in the treatment of a variety of cancers. Here we demonstrated that LDM up-regulates the expression of the tumor suppressor p53 gene by repressing Oct4 transcription. We showed that low dose LDM-induced increase of p53 expression and decrease of Oct4 expression in P19 and HCT116-p53+/+ cells. Knockdown of Oct4 expression by siRNA led to activation of p53 in both cell lines, whereas ectopical expression of Oct4 significantly inhibited p53 expression in P19 cells. LDM-induced p53 activation was blocked by ectopical expression of Oct4.