Succinylation of CTBP1 mediated by KAT2A suppresses its inhibitory activity on the transcription of CDH1 to promote the progression of prostate cancer

Abstract

CTBP1 has been demonstrated as a co-repressor in the transcriptional regulation of downstream genes and is involved in various cell process. However, the mechanism of CTBP1 in the progression of prostate cancer is still unclear. Here, we aim to investigate how CTBP1 exerts its role in prostate cancer progression, especially how CTBP1 was regulated by the upstream genes. We found that CTBP1 was highly expressed in prostate cancer and promoted the cell viability, migration, invasion and glycolysis of prostate cancer cells. CDH1 was verified to be the target of CTBP1. We determined that CTBP1 could directly bind with SP1 to inhibit the transcription of CDH1. Moreover, succinylation of CTBP1 was found to be up-regulated in prostate cancer cell. Further studies demonstrated that KAT2A promotes the succinylation of CTBP1 and mediates the transcription suppressing activity of it. In addition, the K46 and K280 was confirmed to be the two sites that regulated by KAT2A. In vivo studies further indicated that CTBP1 could promote the growth of prostate cancer, and this effect of CTBP1 could be partially reversed by KAT2A knockdown. Taken together, we found that succinylation of CTBP1 mediated by KAT2A suppresses the inhibitory activity of CTBP1 on the transcription of CDH1, thus act as an oncogene.

Keywords: CDH1; CTBP1; KAT2A; Prostate cancer; Succinylation; Transcription.